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.

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.

Bilateral Pattern Electroretinogram Abnormalities in Patients with Herpes Zoster Keratitis and Conjunctivitis.

INTRODUCTION: Herpes zoster ophthalmicus (HZO) results from the reactivation of varicella zoster virus (VZV) in the ophthalmic branch of the trigeminal nerve. The inflammation caused by VZV involves multiple tissues in the eyes. Our goal is to evaluate pattern electroretinogram (PERG) changes and their relationship with corneal sub-basal nerve changes in patients with HZO. METHODS: Twenty-two patients with herpes zoster keratitis or conjunctivitis and 20 healthy volunteers were recruited for this cross-sectional study. A PERG test was performed on both eyes of HZO patients and one eye of the healthy controls. In vivo confocal microscopy (IVCM) was also performed on both eyes of the HZO patients to detect corneal nerve damage. RESULTS: Our results showed changes in the PERG parameters in both eyes of HZO patients compared to the healthy controls. Affected eyes showed delayed N95 peak time and decreased P50 and N95 amplitude compared to the unaffected eyes (p < 0.05, respectively). Both affected and unaffected eyes in HZO patients showed delayed P50 peak time and decreased N95 amplitude (p < 0.05, respectively) compared to controls. In HZO patients, no significant differences in each PERG parameter were found between eyes with and without corneal lesions or between eyes with and without increased Langham's cells in the corneal epithelial sub-basal layer. The IVCM images showed decreased total nerve length and number at the sub-basal layer of the epithelial cornea in affected eyes compared to unaffected eyes (p < 0.05). No significant correlation was found between total nerve length and PERG changes. CONCLUSIONS: Our results showed that VZV-affected eyes without central cornea involvement displayed reduced N95 amplitude and prolonged P50 peak time in bilateral eyes compared to the healthy controls. Larger studies are needed to further explore the effect of HZO on the electrophysiological response of the eye and the posterior segment.

Establishment of a Beagle Dog Model of Dry Eye Disease.

Purpose: To establish a Beagle dog model of dry eye disease (DED). Methods: DED models were induced by surgical removal of orbital lacrimal glands and entire resection of third eyelids in the left eyes of six Beagle dogs. Intact right eyes served as self-controls. Non-anaesthetized Schirmer test (STT), tear break-up time (TBUT), and fluorescein staining grading were performed monthly after operation. Interleukin (IL)-1ß, IL-8, IL-10, and tumor necrosis factor-α (TNF-α) levels were detected in tears and conjunctiva tissues. Six months after surgery, conjunctiva and cornea were collected and histopathologically analyzed. Results: Signs of DED appeared within one month after surgery and then remained stable. STT values were significantly reduced by 88% within 3 weeks after operation and remained stable over months with 1.6 ± 0.4 mm. Mean TBUT decreased significantly within two months after operation and maintained 5.2 ± 1.1 seconds. The mean fluorescein staining score was highest at the first month and then was reduced, eventually reaching a balance with 11.0 ± 1.3 points. Elevated levels of IL-1ß, IL-8, IL-10, and TNF-α were detected in tears and conjunctivas of operated eyes. Hematoxylin and eosin staining showed cornea neovascularization in the corneal stroma with thickened stroma layer and disorganized collagen bundles. Periodic acid-Schiff staining revealed a reduced function of conjunctival goblet cells. Conclusions: A combined type of DED model on the Beagle dog was established by removal of the orbital lacrimal gland and resection of the third eyelid. This DED model is easily accessible and is stable at six-month observation. Translational Relevance: The surgery-induced Beagle dog DED model is easily accessible and stable over a relatively long time.

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.

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.

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.

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.