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.

PurposeAnxiety 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.MethodsThis 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.ResultsAnalysis 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.ConclusionThis 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.

Primary Sjögren's syndrome (pSS) is a chronic, systemic autoimmune disease defined as exocrine gland hypofunction resulting in dry eyes and dry mouth. Recent interest in biological therapies for pSS has been garnered, however achieving FDA-approval has been challenging due to the numerous complications in the trials. Current literature lacks insight and a molecular target-based approach to the development of biological therapies. This review focuses on novel research in newly defined drug targets and latest clinical trials for pSS treatment. A literature search was conducted on ClinicalTrials.gov using the search term “Primary Sjögren's syndrome”. Articles published between 2000 and 2021 in English language were included. Our findings revealed the potential targets for pSS treatment in clinical trials and the most recent advances in understand-ing of molecular mechanisms underlying the pathogenesis of pSS. A prominent gap in current trials is overlooking the treatment of extraglandular symptoms such as fatigue, depression and anxiety which pervade 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 proved the efficacy and safety. Novel therapies may complement existing non-pharmacological methods of alleviating symptoms of pSS. Better grad-ing systems adding extraglandular symptoms to gauge disease activity and severity should be created. The future of pSS therapies may lie in gene therapy, stem cell and tissue engineering ther-apy.

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PurposePrevious 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.MethodsThirty-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.ResultsThe 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).ConclusionsWearing OOK for 2 or more years increased lower eyelid meibomian gland dropout but did not have a reduction of LLT.

PurposeThis 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.MethodsThis 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-1β, 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.ResultsAt 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-1β, IL-13, and CCL11/Eotaxin than the physiotherapy group. TNF-α, CXCL8/IL-8, CXCL10/IP-10, IL-10, EGF, IL-1β, 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.ConclusionsThe 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.

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.

PurposeTo explore the characteristics of spatial-temporal prevalence and public attention of dry eye diseases (DED) through Baidu Index (BI) based on infodemiology method.MethodsThe 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.ResultsThe 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.ConclusionsThe 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.