Metal-Organic Framework-Based Surface-Enhanced Raman Scattering Sensing Platform for Trace Malondialdehyde Detection in Tears.

Disease biomarkers in tears are crucial for clinical diagnosis and health monitoring. However, the limited volume of tear samples, low concentration of tear biomarkers, and complex tear composition present challenges for precise testing. We introduce a spot-on testing platform of metal-organic framework (MOF)-based surface-enhanced Raman scattering (SERS) capillary column, which is capable of target molecules selective separation and enrichment for tear biomarkers in situ detection. It consists of Au nanostars for effective SERS signal and a porous MOF shell for separating impurities through molecular sieving effect. This platform allows for simultaneous collection and detection of tear, capturing the disease biomarker malondialdehyde in tears with a 9.38 × 10-9 mol/L limit of detection. Moreover, we designed a hand-held device based on this tubular SERS sensor, successfully diagnosing patients with dry eye disease. This functional capillary column enables noninvasive and rapid diagnosis of biomarkers in biofluids, providing potential for disease diagnosis and healthcare monitoring.

Salivary Gland Transplantation as a Promising Approach for Tear Film Restoration in Severe Dry Eye Disease.

With increased awareness of dry eye disease (DED), a multitude of therapeutic options have become available. Nevertheless, the treatment of severe DED remains difficult. In a patient whose DED is related to the loss of lacrimal function without severe destruction of the salivary glands, autologous transplantation of the latter as functioning exocrine tissue to rebuild a stable tear film is an attractive idea. All three major and minor salivary glands have been used for such transplantation. Due to the complications associated with and unfavorable prognosis of parotid duct and sublingual gland transplantation, surgeons now prefer to use the submandibular gland (SMG) for such procedures. The transplantation of the SMG not only has a high survival rate, but also improves dry eye symptoms and signs for more than 20 years post-surgery. The regulation of the secretion of the transplanted SMG is critical because the denervated SMG changes its mechanism of secretion. Innovative procedures have been developed to stimulate secretion in order to prevent the obstruction of the Wharton's duct and to decrease secretion when postoperative "epiphora" occurs. Among the minor salivary glands, the transplantation of the labial salivary glands is the most successful in the long-term. The measurement of the flow rates of minor salivary glands and donor-site selection are critical steps before surgery.

The Future of Targeted Treatment of Primary Sjögren's Syndrome: A Focus on Extra-Glandular Pathology.

Primary Sjögren's syndrome (pSS) is a chronic, systemic autoimmune disease defined by exocrine gland hypofunction resulting in dry eyes and dry mouth. Despite increasing interest in biological therapies for pSS, achieving FDA-approval has been challenging due to numerous complications in the trials. The current literature lacks insight into a molecular-target-based approach to the development of biological therapies. This review focuses on novel research in newly defined drug targets and the latest clinical trials for pSS treatment. A literature search was conducted on ClinicalTrials.gov using the search term "Primary Sjögren's syndrome". Articles published in English between 2000 and 2021 were included. Our findings revealed potential targets for pSS treatment in clinical trials and the most recent advances in understanding the molecular mechanisms underlying the pathogenesis of pSS. A prominent gap in current trials is in overlooking the treatment of extraglandular symptoms such as fatigue, depression, and anxiety, which are present in most patients with pSS. Based on dryness and these symptom-directed therapies, emerging biological agents targeting inflammatory cytokines, signal pathways, and immune reaction have been studied and their efficacy and safety have been proven. Novel therapies may complement existing non-pharmacological methods of alleviating symptoms of pSS. Better grading systems that add extraglandular symptoms to gauge disease activity and severity should be created. The future of pSS therapies may lie in gene, stem-cell, and tissue-engineering therapies.

Evaluation of the Effects of Pterygium and Aging on Limbal Structure Using Optical Coherence Tomography.

Previous studies suggest that regions of corneal limbus may possess structural differences. We aimed to investigate the limbal changes associated with pterygium and aging via optical coherence tomography (OCT). Palisades of Vogt epithelial thickness (POV-ET) and Bowman's membrane epithelial thickness (BM-ET) were measured at the nasal, temporal, superior, and inferior quadrants of patients with pterygium and healthy subjects of different ages. Values were expressed as a ratio that functioned as an index used to evaluate the change of limbus. Ratio values determined for quadrants of the corneal limbus were correlated highly in young healthy subjects. Further, parameter values were significantly greater than those of elder healthy subjects. In young subjects, the temporal and superior quadrants of patients with pterygium were significantly lower than those of healthy subjects. Temporal and superior quadrants of elder pterygium patients affected by both pterygium and age were significantly lower than those of healthy subjects; however, the inferior quadrant of elderly pterygium patients was significantly higher than that of age-matched healthy subjects. Our findings revealed that the thickness of limbal epithelium was negatively correlated with age, while pterygium led to the thinning of the temporal and superior limbal epithelium and inferior limbal epithelial thickening.

Response of tear cytokines following intense pulsed light combined with meibomian gland expression for treating meibomian gland dysfunction-related dry eye.

Purpose: This study compared the changes in tear inflammatory cytokine levels after intense pulsed light (IPL) combined with meibomian gland expression (MGX) (IPL group) and instant warm compresses combined with MGX (physiotherapy group) as treatments for meibomian gland dysfunction (MGD)-related dry eye disease (DED) to explore their similarities and differences in therapeutic mechanisms. Methods: This study was a post-hoc analysis of a randomized controlled trial. Thirteen patients with MGD-related DED were enrolled in each group and received three treatments correspondingly with 3-week intervals. The levels of 20 tear cytokines, namely, TNF-α, IL-6, MMP-9, CXCL8/IL-8, CXCL10/IP-10, IL-10, EGF, IL-6R, IL-1ß, IFN-γ, lactoferrin, Fas ligand, IL-17A, LT-α, S100A9, LCN2/NGAL, IL-13, IL-12/IL-23p40, Fas, and CCL11/Eotaxin, were measured at baseline, before the second and third treatments, and 3 weeks after the third treatment. The primary outcome was the difference in cytokine levels between baseline and the last measurement, and the trends were analyzed at each measurement point. Results: At the last measurement, a significant decrease was observed in all tear cytokines for both IPL and physiotherapy groups compared with baseline. The IPL group showed greater reductions in IL-6, IL-6R, IL-1ß, IL-13, and CCL11/Eotaxin than the physiotherapy group. TNF-α, CXCL8/IL-8, CXCL10/IP-10, IL-10, EGF, IL-1ß, IFN-γ, and Lipocalin-2/NGAL levels continued to decrease with treatment time. Important interactions were found in the changes of IL-6 and IL-13 levels, where the levels first decreased and then slightly increased in the physiotherapy group after treatment, while they continued to decrease in the IPL group. Conclusions: The mechanisms of IPL and physiotherapy in treating MGD-related DED were both associated with reducing inflammation, and the superiority of IPL could be attributed to its better inhibitory effect on inflammatory cytokines like IL-6. In addition, several cytokines were on a downward trend during treatment, suggesting that the vicious cycle of DED was suppressed.

Decrease in Tear Film Lipid Layer Thickness in Patients with Keratoconus.

Keratoconus (KC) is a progressive corneal disorder characterized by thinning and protrusion, mostly of the inferotemporal and central corneal regions. Dysfunction of the meibomian gland, the excretions of which form the lipid layer of the tear film, has been reported to be associated with KC. Thus, this manuscript investigates the correlation among lipid layer thickness (LLT), partial blink rate (PBR), and KC of different degrees. This retrospective study included 54 patients and 24 healthy controls. The anterior corneal curvature, LLT, and PBR were taken from the unilateral eye of all 78 participants. The difference in those ocular parameters between the moderate and severe groups and the control group is significant. No significant association was found between anterior corneal curvature and LLT (r = −0.2, p = 0.15) across all the patients. However, there was a significant negative correlation between anterior corneal curvature and LLT in moderate (r = −0.6, p < 0.05) and severe (r = −0.7, p < 0.05) keratoconus cases. The results also show a significant negative correlation between anterior corneal curvature and PBR (r = −0.41, p < 0.05). Therefore, we conclude that the severity of keratoconus is associated with the thinning of LLT and the reduction of PBR. This may relate to a further epithelial abnormality with the reduced protection of tear film from the air, leading to the release of proteolytic enzymes that degrade stromal collagen and weaken the cornea.

Utilizing Baidu Index to Investigate Seasonality, Spatial Distribution and Public Attention of Dry Eye Diseases in Chinese Mainland.

Purpose: To explore the characteristics of spatial-temporal prevalence and public attention of dry eye diseases (DED) through Baidu Index (BI) based on infodemiology method. Methods: The data about BI of DED were collected from Baidu search engine using "Dry eye diseases" as keyword. The spatial and temporal distribution of DED were analyzed through timeseries data decomposition as well as spatial autocorrelation and hotspot detection of BI about DED. The most popular related words and demographic characteristics were recorded to determine the public attention of DED. Results: The trends of BI about DED in Chinese mainland had gradually increased over time with a rapid increase from 2012 to 2014 and in 2018. The results of timeseries decomposition indicated that there was seasonality in the distribution of BI about DED with the peak in winter, especially in northern regions. The geographic distribution demonstrated the search activities of DED was highest in the east of Chinese mainland while lowest in the west. The vast majority of people searching for DED were teenagers (20-29 years), with a predominance of females. Glaucoma, keratitis and conjunctivitis were the diseases most often confused with DED, and the artificial tears were the most common treatment for DED in Chinese mainland according to the BI about DED. Conclusions: The analysis revealed the seasonality, geographic hotspots and public concern of DED through BI in Chinese mainland, which provided new insights into the epidemiology of DED.

Experience of Dry Eye Patients With Anxiety and Depression: A Qualitative Study.

Purpose: Anxiety and depression are important risk factors for dry eye disease (DED). The aims of this research are to identify the cause of anxiety and depression in DED patients and explore their strategies in coping with DED. Methods: This is a qualitative study based on semi-structured interviews, and the interviews records were analyzed through inductive thematic analysis. Participants were recruited from a large university affiliated hospital in the north of China, including 47 participants affected by depression and anxiety. Results: Analysis revealed the causes of anxiety and depression in DED patients could be divided into three major themes and nine subthemes: (1) From hospital: including difficulties in diagnosing and seeking medical advice, neglect or lack of attention from clinicians, low treatment satisfaction and complex comorbidities; (2) From daily life: including life satisfaction and well-being, changes in lifestyle pattern and changes in workstyle pattern; (3) From society: including burden of disease and reduction of social interaction. Most DED Patients with anxiety and depression were more likely to face the condition as well as receive treatments negatively, while the others tended to seek treatments unduly and blindly. Conclusion: This investigation offers new insights into the understanding difficulties in DED patients with anxiety and depression, and provides valuable guidance for supporting them to reduce depression and anxiety as well as improve prognosis.

Orthokeratology Lens Wear for 2 Years in Children Did Not Alter Tear Film Lipid Thickness by Non-Invasive Interferometry.

PURPOSE: Previous studies suggest that overnight orthokeratology (OOK) may be detrimental to tear function. We aimed to investigate the effect of OOK on lipid layer thickness (LLT), blink pattern, and meibomian gland and elucidate the relationship of these variables. METHODS: Thirty-seven participants who wore OOK lenses every night for at least 2 years and twenty-four healthy non-contact lens wearers (controls) were enrolled in this retrospective study. LipiView interferometry, blink pattern analysis, the ocular surface status, and morphology and function of the meibomian gland were determined. RESULTS: The OOK group and healthy controls had similar LLT, blink patterns, ocular surface status, and the function of the meibomian gland. OOK participants demonstrated higher meiboscore in the lower eyelids (p < 0.05) but not in the upper eyelids. Within the OOK group, LLT was significantly impacted by the partial blink rate (p < 0.05) and the total score of the upper meibomian gland (p = 0.10). CONCLUSIONS: Wearing OOK for 2 or more years increased lower eyelid meibomian gland dropout but did not have a reduction of LLT.

Therapeutic Effects of Melatonin on Ocular Diseases: Knowledge Map and Perspective.

Melatonin plays a critical role in the pathophysiological process including circadian rhythm, apoptosis, and oxidative stress. It can be synthesized in ocular tissues, and its receptors are also found in the eye, triggering more investigations concentrated on the role of melatonin in the eye. In the past decades, the protective and therapeutic potentials of melatonin for ocular diseases have been widely revealed in animal models. Herein, we construct a knowledge map of melatonin in treating ocular diseases through bibliometric analysis and review its current understanding and clinical evidence. The overall field could be divided into twelve topics through keywords co-occurrence analysis, in which the glaucoma, myopia, and retinal diseases were of greatest research interests according to the keywords burst detection. The existing clinical trials of melatonin in ocular diseases mainly focused on the glaucoma, and more research should be promoted, especially for various diseases and drug administration. We also discuss its bioavailability and further research topics including developing melatonin sensors for personalized medication, acting as stem cell therapy assistant drug, and consuming food-derived melatonin for facilitating its clinical transformation.

Synthesis of a Lignin-Fe/Mn Binary Oxide Blend Nanocomposite and Its Adsorption Capacity for Methylene Blue.

A high-performance modified lignin adsorbent was prepared through coprecipitation of ferrous, ferric, and permanganate with lignin in sodium hydroxide solution. The structural characteristics of the synthesized lignin-Fe/Mn binary oxide blend nanocomposite (L-F/M) and its performance on the methylene blue (MB) removal from aqueous solution were evaluated. Influence factors of adsorption effects were analyzed including pH, contact time, dye concentration, temperature, and thermodynamics. The pseudo-second-order kinetic model well described the adsorption kinetics, and the adsorption isotherms best fitted the Langmuir model with a maximum adsorption capacity of 252.05 mg g-1 at 298 K. The adsorption mechanism showed that the L-F/M introduced the metallic element and negative charges to the lignin surface, which improved the adherence of MB via hydrogen bonding, electrostatic interaction, and coordination. Moreover, the removal ratio of MB maintained 81.2% after being used in five adsorption-desorption cycles. Results indicated that the L-F/M obtained was an efficient candidate for dye wastewater treatment.

COVID-19 Changed Prevalence, Disease Spectrum and Management Strategies of Ocular Trauma.

The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the health of people around the world and has reshaped social behaviors and clinical practice. The purpose of this perspective is to provide epidemiologists and clinicians with information about how the spectrum of ocular trauma diseases changed, as well as to optimize management for improving patient prognosis during this crisis. Analysis of current studies revealed that the prevalence of eye trauma decreased overall, with a trend of delayed medical treatment during the COVID-19 era. Irregular epidemic prevention and control measures, unprotected home activities, and unusual mental states are the main causes of ocular trauma. Strategies for reducing morbidity are also discussed, including popularizing the use norms of prevention and control supplies, taking heed to the safety of family activities, highlighting the special status of child protection, and paying attention to previous case data to implement region-specific precautions. The procedure of ophthalmological emergency and outpatient management should also be optimized, and mental health should be emphasized during this pandemic.

Polysaccharide-Based Nanomaterials for Ocular Drug Delivery: A Perspective.

Ocular drug delivery is one of the most challenging issues in ophthalmology because of the complex physiological structure of the eye. Polysaccharide-based nanomaterials have been extensively investigated in recent years as ideal carriers for enhancing the bioavailability of drugs in the ocular system because of their biocompatibility and drug solubilization. From this perspective, we discuss the structural instability of polysaccharides and its impact on the synthesis process; examine the potential for developing bioactive polysaccharide-based ocular drug nanocarriers; propose four strategies for designing novel drug delivery nanomaterials; and suggest reviewing the behavior of nanomaterials in ocular tissues.

Catalytic pyrolysis of poplar sawdust: Excellent hydrocarbon selectivity and activity of hollow zeolites.

Hollow zeolites were investigated for catalytic fast pyrolysis (CFP) of biomass to produce hydrocarbon-rich bio-oil. A series of hollow ZSM-5 catalysts were synthesized via a dissolution-recrystallization strategy. The physicochemical properties of the catalysts were investigated by high-resolution transmission electron microscopy, N2 sorption, X-ray photoelectron spectroscopy, and ammonia temperature-programmed desorption experiments. The hollow zeolite was effective for increasing the hydrocarbon fraction in bio-oil. In particular, hollow HS-ZSM-5(50) afforded the highest hydrocarbon yield (6.8 wt%), which was ~3 times of that achieved with solid ZSM-5(50). The hollowness, acidity, and the presence of secondary wall mesopores in the hollow zeolite were found to affect bio-oil production. The hollow regions stabilized more active biomass intermediates and inhibited their repolymerization to coke, while the interior acid sites continually converted these intermediates to aromatic hydrocarbons. Secondary wall mesopores compromise the hollow space and hinder consecutive catalysis, resulting in phenols as the main product.