Dual‑Atom Nanozyme Eye Drops Attenuate Inflammation and Break the Vicious Cycle in Dry Eye Disease

Dry eye disease(DED)is a major ocular pathology worldwide,causing serious ocular discomfort and even visual impairment.The incidence of DED is gradually increasing with the highfrequency use of electronic products.Although inflammation is core cause of the DED vicious cycle,reactive oxygen species(ROS)play a pivotal role in the vicious cycle by regulating inflammation from upstream.Therefore,current therapies merely targeting inflammation show the failure of DED treatment.Here,a novel dual-atom nanozymes(DAN)-based eye drops are developed.The antioxidative DAN is successfully prepared by embedding Fe and Mn bimetallic single-atoms in N-doped carbon material and modifying it with a hydrophilic polymer.The in vitro and in vivo results demonstrate the DAN is endowed with superior biological activity in scavenging excessive ROS,inhibiting NLRP3 inflammasome activation,decreasing proinflammatory cytokines expression,and suppressing cell apoptosis.Consequently,the DAN effectively alleviate ocular inflammation,promote corneal epithelial repair,recover goblet cell density and tear secretion,thus breaking the DED vicious cycle.Our findings open an avenue to make the DAN as an intervention form to DED and ROSmediated inflammatory diseases.

Different concentrations of hyaluronic acid eye drops for dry eye syndrome: a systematic review and Meta-analysis

AIM:To compare high or low concentration of hyaluronic acid eye drops(HY)for dry eye syndromes(DES).METHODS:Randomized controlled trials(RCTs)comparing various concentrations of HY were searched in PubMed,Embase,Web of Science,Cochrane,SinoMed,CNKI,Wanfang Database,CQVIP,and Chinese journals databases between inception and July 2023.Pooled standardized mean differences(SMD)or weighted mean difference(WMD)with 95%confidence intervals(CI)from RCTs evaluating Schirmer’s I test(SIT),corneal fluorescein staining score(CFS),tear breakup time(TBUT),DES score(DESS),and Ocular Surface Disease Index(OSDI)were calculated.Sensitivity analysis,Egger’s test and Meta-regression analysis were performed for all indicators.RESULTS:We conducted a Meta-analysis of 10 RCTs that met the inclusion criteria,involving 1796 cases.High-concentrations group significantly improved the outcome of CFS according to random effects modelling(SMD,-3.37;95%CI,-5.25 to-1.48;P=0.0005).The rest of the results were not statistically significant,including indicators such as SIT,TBUT,DESS and OSDI.CONCLUSION:For dry eyes with positive corneal staining,a high concentration of HY is recommended,whereas in other cases,a high concentration of HY does not offer a more pronounced advantage over a low concentration of HY in the treatment of dry eyes.

Evaluation of dry eye disease symptomatology and mental health status among patients with different COVID-19 statuses

AIM:To evaluate dry eye disease(DED)symptomatology and mental health status in different COVID-19 patients.METHODS:A cross-sectional observational design was used.Totally 123 eligible adults(46.34%of men,age range,18-59y)with COVID-19 included in the study from August to November,2022.Ocular Surface Disease Index(OSDI),Five-item Dry Eye Questionnaire(DEQ-5),Hospital Anxiety and Depression Scale(HADS),and Pittsburgh Sleep Quality Index(PSQI)were used in this study.RESULTS:OSDI scores were 6.82(1.25,15.91)in asymptomatic carriers,7.35(2.50,18.38)in mild cases,and 16.67(4.43,28.04)in recurrent cases,with 30.00%,35.56%,and 57.89%,respectively evaluated as having DED symptoms(χ2=7.049,P=0.029).DEQ-5 score varied from 2.00(0,6.00)in asymptomatic carriers,3.00(0,8.00)in mild cases,and 8.00(5.00,10.00)in recurrent cases,with 27.50%,33.33%,and 55.26%,respectively assessed as having DED symptoms(χ2=8.532,P=0.014).The prevalence of clinical anxiety(50.00%)and depression(47.37%)symptoms were also significantly higher in patients with recurrent infection(χ2=24.541,P<0.001;χ2=30.871,P<0.001).Recurrent infection was a risk factor for high OSDI scores[odds ratio,2.562;95%confidence interval(CI),1.631-7.979;P=0.033]and DEQ-5 scores(odds ratio,3.353;95%CI,1.038-8.834;P=0.043),whereas having a fixed occupation was a protective factor for OSDI scores(odds ratio,0.088;95%CI,0.022-0.360;P=0.001)and DEQ-5 scores(odds ratio,0.126;95%CI,0.039-0.405;P=0.001).CONCLUSION:Patients with recurrent COVID-19 have more severe symptoms of DED,anxiety,and depression.

Dry eye rate and its relationship with disease stage in patients with primary hypertension:a cross-sectional study in Vietnam

AIM:To determine the dry eye(DE)rate and its relationship with disease stage in patients with primary hypertension.METHODS:A cross-sectional study included 432 patients with primary hypertension(with an equal number of patients in each group:144 in stage Ⅰ,Ⅱ,and Ⅲ hypertension)and 144 healthy subjects as a control group.The Ocular Surface Disease Index(OSDI)and Schirmer Ⅰ test without anesthetics were conducted on all 576 subjects.Subjects with OSDI scores<13 and Schirmer Ⅰ values equal to or under 10 mm were diagnosed with DE.RESULTS:The ratio of DE in hypertension patients was higher than in the control group(41.7%versus 18.8%;P<0.001).The proportion of patients with DE increased gradually according to the hypertension stage:27.1% in stage Ⅰ,40.3% in stage Ⅱ,and 57.6% in stage Ⅲ,P<0.001.Age,duration of hypertension,plasma urea,creatinine,and high-sensitivity C-reactive protein(CRP-hs)levels in hypertension patients with DE were higher than those without DE,P<0.001.Advanced age,a long duration of hypertension,diabetes mellitus,elevated plasma creatinine,and CRP-hs levels were independent factors associated with DE in primary hypertension patients,P<0.001.CONCLUSION:DE is a common disorder associated with advanced age,a long duration of hypertension,diabetes mellitus,elevated plasma CRP-hs,and creatinine levels in patients with primary hypertension.

Dry eye disease in systemic lupus erythematosus: a cross sectional study

AIM:To explore ocular surface manifestations of dry eye disease(DED)and its influencing factors in systemic lupus erythematosus(SLE)patients.METHODS:Ophthalmological examinations were conducted in SLE patients(n=43)and controls(n=41),including Ocular Surface Disease Index(OSDI),objective scatter index(OSI),tear meniscus height(TMH),lipid layer thickness(LLT),non-invasive Keratograph tear breakup time(NIKBUT),corneal fluorescein score(CFS),Schirmer I test.DED was diagnosed according to the Tear Film and Ocular Surface Society Dry Eye Workshop II Criteria.SLE patients were further divided into DED group and non-DED group,the disease activity,clinical manifestations and laboratory investigations were compared between the two groups.The disease activity was evaluated by Systemic Lupus Erythematosus Disease Activity Index 2000(SLEDAI-2K).Receiver operative characteristic(ROC)curve and multiplefactor binary logistic regression were performed.RESULTS:SLE patients showed higher OSDI[9.1(2.8-15.9)vs 6.3(2.2-7.5),P=0.035],higher OSI[1.67(1.09-2.60)vs 0.96(0.87-1.60),P=0.001],higher CFS[1(0-2)vs 0(0-1),P=0.001],lower LLT[65(42-100)vs 100(79.5-100),P=0.010],and lower NIKBUT[8.03(4.02-9.73)vs 9.67(5.26-12.71),P=0.030]than controls.The 32.6%of SLE patients had DED,which was higher than 12.2%of healthy controls.DED group showed higher SLEDAI-2K score[9.7±6.1 vs 5.4±3.4,P=0.025],higher anti-cardiolipin antibody(ACL)[8.7(3.5-13.2)vs 3.6(2.0-6.9),P=0.035],and higher proportion of patients with cutaneous eruption[42.9%vs 6.9%,P=0.015]than non-DED group.According to multiple-factor binary logistic regression analysis,the SLEDAI-2K score(OR=1.194,P=0.041)and cutaneous eruption(OR=7.094,P=0.045)could be consider as risk factors for DED in SLE patients.The ROC curve of the combined factors including age,disease duration,SLEDAI-2K score,ACL,and cutaneous eruption was analyzed,with a sensitivity of 0.786,a specificity of 0.793,and an area under curve of 0.820.CONCLUSION:Ocular surface affection is frequent in SLE patients,and patients with high disease activity and cutaneous eruption show increased risk of DED.

Analyze interleukin-1β,interleukin-6,and tumor necrosis factor-αlevels in dry eye and the therapeutic effect of cyclosporine A

BACKGROUND Dry eye is a common eye disease.Artificial tears supplements are widely used for the treatment of dry eyes.However,multiple adverse effects have been observed in patients receiving long-term treatment with artificial tears,which may affect the therapeutic effect.AIM To analyze the characteristics of interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-alpha(TNF-α)levels in patients with dry eye and the therapeutic effect of artificial tears combined with cyclosporine A.METHODS A total of 124 dry eye patients treated at The First People’s Hospital of Xining from April 2020 to April 2022 were selected as the observation group,while 20 healthy individuals served as the control group during the same period.Levels of inflammatory markers,including IL-1β,IL-6,and TNF-α,were analyzed.The observation group was further divided into a study group and a control group,each consisting of 62 patients.The control group received artificial tears,whereas the study group received a combination of artificial tears and cyclosporine A.Inflammatory markers,Schirmer’s test(SIT),tear break-up time(TBUT),corneal fluorescein staining(CFS),National Eye Institute Visual Function Questionnaire-25(NEI-VFQ-25)scores,and adverse events(AEs)were compared between the two groups.RESULTS The observation group exhibited significantly elevated serum levels of IL-1β,IL-6,and TNF-αin comparison to the healthy group.Following treatment,the study group demonstrated substantial reductions in IL-1β,IL-6,and TNF-αlevels relative to the control group.Moreover,after treatment,the study group experienced a marked decrease in CFS scores and significant increases in both SIT and BUT levels when compared to the control group.Additionally,significant improvements were observed in the primary symptom of dry eye and secondary symptoms such as photophobia,foreign body sensation,fatigue,red eye,and burning sensation within the study group.Furthermore,post-treatment NEI-VFQ-25 scores across all dimensions exhibited significant enhancements in the study group compared to the control group(P<0.05).It is noteworthy that significant AEs were reported in both groups throughout the treatment period.CONCLUSION Cyclosporine A combined with artificial tears is effective in treating dry eye,yielding enhanced outcomes by improving SIT and TBUT levels,reducing CFS scores,and ameliorating vision-related quality of life.

Effect of the traditional Chinese medicine fumigation combined with the meibomian gland squeezer for treatment of dry eye associated with meibomian gland dysfunction

Background:To observe the effect of traditional Chinese medicine fumigation combined with the meibomian gland squeezer for the treatment of dry eye associated with meibomian gland dysfunction(MGD).Methods:This is a randomized,controlled,non-masked,single-center study.Seventy-four cases(74 eyes)of dry eye associated with MGD were randomly divided into two groups.Thirty-seven patients were chosen as the treatment group was treated by the traditional Chinese medicine fumigation 3 times a week combined with the meibomian gland squeezer once a week for one month.The other 37 cases were sorted as the control group and only treated with the meibomian gland squeezer once a week for one month.Both groups received the primary treatment for 1 month,including Tobradex eye ointment once a day and 0.1%sodium hyaluronate eye drops 4-6 times daily.Patients were evaluated at baseline and 2-week and 1-month visits for the ocular symptom scores,international ocular surface disease index(OSDI),fluorescein tear break-up time(TBUT),corneal fluorescein staining test(CFS),Schirmer I test,meibum quality and meibum expressibility.Results:Sixty-seven patients were followed in the study,and the mean age was 57(±12.6)years.Thirty-three patients(11 males)in the treatment group and 34 patients(8 males)in the control group were followed in the study,and the mean age of the two groups was 45.36±15.02 years and 43.68±13.43 years,respectively.Before treatment,there was no significant difference between the two groups in gender,age,ocular symptom scores,OSDI,TBUT,CFS,Schirmer I test,meibum quality,and meibum expressibility(P>0.05).Compared with baseline,the 2 groups had different degrees of improvement in the ocular symptom scores,OSDI,TBUT,CFS,meibum quality,and meibum expressibility at the 2-week and 1-month visits(P<0.05),and the treatment group showed a more significant improvement in the ocular symptom scores,OSDI,TBUT,CFS,meibum quality and meibum expressibility compared with the control group(P<0.05).In addition,no serious adverse events were observed in each group.Conclusions:The traditional Chinese medicine fumigation combined with the meibomian gland squeezer may be safe,effective,and helpful for the treatment of dry eye associated with MGD.

Lid scrubbing with a gel combining natural extracts for dry eye treatment

AIM:To evaluate the effect of lid scrubbing using a gel combining different natural extracts on ocular signs and symptoms of dry eye patients.METHODS:A retrospective study was performed on 19 dry eye patients(51.1±16.0y).Non-invasive tear break-up time,tear meniscus height,meibomian gland loss,lipid layer thickness,conjunctival redness,corneal staining,ocular surface disease index(OSDI),and ocular pain intensity were measured before(baseline),1wk,and 2mo after lid scrubbing with a gel containing different natural extracts(okra extract,aloe vera leaf juice,hydrolysed soy protein,caffeine,citrus unshiu peel extract,and raspberry seed oil).RESULTS:Compared with the baseline,there was a statistically significant improvement in both first(P=0.048)and average(P=0.026)non-invasive tear break-up time 2mo after treatment,as well as in corneal staining(P=0.043,0.012),OSDI(P<0.001),and ocular pain intensity(P<0.001)after 1wk and 2mo.In addition,there was no correlation between ocular signs and symptoms.CONCLUSION:The lid scrubbing with a gel combining different natural extracts show beneficial effects on tear film stability,corneal damage,and ocular symptoms,which is the reason why this therapeutic procedure is proposed as an alternative for dry eye management.However,it is not possible to attribute this beneficial effect solely to the presence of the natural extracts in the gel,primarily due to the absence of a negative control group.

Rabbit models of dry eye disease: comparative analysis

AIM:To report ocular changes in rabbits after the implementation of three different induction methods to create dry eye(DE)conditions and provides evidence of DErelated disease evolution.METHODS:Experimental methods were divided into 3 models.The first model used involved triple injection of complete Freund’s adjuvant,50µL each,also called the meibomian gland dysfunction(MGD)model.In the second model,DE conditions were created by the resection of nictitating membranes(NM),Harderian glands(HG),and main lacrimal glands(LG),also called the LGR model.The third model involved the topical administration of benzalkonium chloride(BAK)0.1%solution.The Schirmer test,ocular surface staining with fluorescein,and tear breakup time tests were implemented before and after excision.After euthanasia,the ocular tissues were dissected.Cornea,conjunctiva,and meibomian glands were treated with periodic acid–Schiff(PAS)staining and haematoxylin–eosin staining.RESULTS:The MGD model triggered inflammation of meibomian glands.It detected changes in the lipid layer of the tear film.The bilateral resection of NM,HG,and LG reduced the watering layer of the tear film.The topical administration of BAK of 0.1%solution impacted the mucosal layer of the tear film.CONCLUSION:Different changes are observed with different DE syndrome models.The composition of the tear film differ depending on which part of the eye is targeted.More studies need to be done to confirm whether an increased thickness of the cornea has any impact on the DE disease.

Effects of diquafosol sodium in povidone iodine-induced dry eye model

AIM:To investigate the effects of diquafosol sodium(DQS)for dry eye model induced with povidone-iodine(PI)solution.METHODS:Ten Sprague Dawley rats as the control group.Thirty Sprague Dawley rats were used to establish the dry eye model with stimulation of 10 g/L PI for 14d,then divided rats into three groups:dry eye group with no treatment(DED group,n=10);phosphate buffer saline treated group(PBS group,n=10);diquafosol treated group(DQS group,n=10).Clinical changes were observed by tear production test,fluorescein staining,tear breakup time(TBUT)test,corneal confocal microscope and ocular surface comprehensive analyzer.Eyeballs were collected on day 10 of treatment for hematoxylin-eosin(HE),periodic acid-Schiff(PAS),and alcian blue staining.TUNEL assay,polymorphonuclear(PMN)and mucin 1(MUC1)immunofluorescence were performed and corneal ultrastructural changes were detected by electron microscopy.RESULTS:Compared with DED and PBS groups,tear production(7.26±0.440 vs 4.07±0.474 mm;7.26±0.440 vs 3.74±0.280 mm;all P<0.01)and TBUT(7.37±0.383s vs 1.49±0.260s;7.37±0.383s vs 1.42±0.437s;all P<0.01)were significantly increased in DQS group.HE,PAS,and alcian blue staining and MUC1 immunofluorescence showed mucins and conjunctival goblet cells density(8.45±0.718 vs 5.21±0.813 cells/0.1 mm^(2);8.45±0.718 vs 5.36±0.615 cells/0.1 mm^(2);all P<0.01)increased in DQS group.Confocal microscopy,PMN immunofluorescence and TUNEL staining showed inflammatory infiltration and corneal epithelial cells apoptosis decreased in DQS group.The increased number of microvilli in corneal epithelial and the recovered cell junction were observed in DQS group.CONCLUSION:PI instillation can induce goblet cells and mucin loss,epithelial cell apoptosis and inflammation,which are consistent with the pathological manifestations of dry eye.Diquafosol can repair the ocular surface damage caused by PI,reduce corneal inflammation,inhibit corneal epithelial cell apoptosis,promote mucin secretion and maintain tear film stability.

A combined treatment for patients with dry eye and associated laryngopharyngeal reflux:a real-life approach

AIM:To evaluate the efficacy and tolerability of administering a combined therapy in patients with dry eye syndrome(DES)and associated laryngopharyngeal reflux(LPR).METHODS:The study was retrospective,open,observational,and conducted in a real-life setting.Patients had pathological symptom assessment in dry eye(SANDE)and reflux symptom index(RSI)at baseline.Patients were re-assessed after 1mo and at the end of treatment.The treatment consisted of a three-month course based on the combined therapy:Gastroftal eye drops,one drop three times a day,and Gastroftal tablets,two tablets after lunch and two tablets after dinner.Tear break-up-time(TBUT)test,Schirmer test,RSI,and SANDE questionnaire were evaluated.RESULTS:The study included 253 patients.The mean age was 58±11.19y.TBUT test score and Schirmer’s test significantly increased(both P<0.001)after 1mo and at the end of treatment.The RSI score and SANDE scores significantly decreased(both P<0.001)after 1mo and at the end of treatment.CONCLUSION:The current,retrospective,and open study shows that combined therapy using Gastroftal eye drops and tablets could represent a valuable option in managing patients with DES associated with LPR.

Role of lymphotoxin alpha as a new molecular biomarker in revolutionizing tear diagnostic testing for dry eye disease

Dry eye disease(DED),primarily classified as multifactorial ocular surface disorder,afflicts tens of millions of individuals worldwide,adversely impacting their quality of life.Extensive research has been conducted on tear film analysis over the past decades,offering a range of tests to evaluate its volume,health,and integrity.Yet,early diagnosis and effective treatment for DED continue to pose significant challenges in clinical settings.Nevertheless,by recognizing key phenomena in DED such as ocular surface inflammation,hyperosmolarity,and tear film instability,this article provides a comprehensive overview of both traditional and recently developed methods for diagnosing and monitoring DED.The information serves as a valuable resource not only for clinical diagnosis but also for further research into DED.

Analysis of postoperative ocular surface changes and intervention effect after pars plana vitrectomy in meibomian gland dysfunction dry eye patients

AIM:To observe ocular surface changes after phacovitrectomy in patients with mild to moderate meibomian gland dysfunction(MGD)-type dry eye and track clinical treatment response using a Keratograph 5M and a Lipi View interferometer.METHODS:Forty cases were randomized into control group A and treatment group B;the latter received meibomian gland treatment 3d before phacovitrectomy and sodium hyaluronate before and after surgery.The average non-invasive tear film break-up time(NITBUTav),first noninvasive tear film break-up time(NITBUTf),non-invasive measured tear meniscus height(NTMH),meibomian gland loss(MGL),lipid layer thickness(LLT)and partial blink rate(PBR)were measured preoperatively and 1wk,1 and 3mo postoperatively.RESULTS:The NITBUTav values of group A at 1wk(4.38±0.47),1mo(6.76±0.70),and 3mo(7.25±0.68)were significantly lower than those of group B(7.45±0.78,10.46±0.97,and 11.31±0.89;P=0.002,0.004,and 0.001,respectively).The NTMH values of group B at 1wk(0.20±0.01)and 1mo(0.22±0.01)were markedly higher than those of group A(0.15±0.01 and 0.15±0.01;P=0.008 and P<0.001,respectively);however,there was no difference at 3mo.The LLT of group B at 3mo[91.5(76.25-100.00)]significantly exceeded that of group A[65.00(54.50-91.25),P=0.017].No obvious intergroup difference was found in MGL or PBR(P>0.05).CONCLUSION:Mild to moderate MGD dry eye worsens in the short term after phacovitrectomy.Preoperative cleaning,hot compresses,and meibomian gland massage as well as preoperative and postoperative sodium hyaluronate promote the rapid recovery of tear film stability.

Dynamic tear meniscus parameters in complete blinking:insights into dry eye assessment

AIM:To investigate the relationship between dynamic tear meniscus parameters and dry eye using an automated tear meniscus segmentation method.METHODS:The analysis of tear meniscus videos captured within 5s after a complete blink includes data from 38 participates.By processing video data,several key parameters including the average height of the tear meniscus at different lengths,the curvature of the tear meniscus’s upper boundary,and the total area of the tear meniscus in each frame were calculated.The effective values of these dynamic parameters were then linearly fitted to explore the relationship between their changing trends and dry eye disease.RESULTS:In 94.74%of the samples,the average height of central tear meniscus increased over time.Moreover,97.37%of the samples exhibited an increase in the overall tear meniscus height(TMH)and area from the nasal to temporal side.Notably,the central TMH increased at a faster rate compared to the nasal side with the temporal side showing the slowest ascent.Statistical analysis indicates that the upper boundary curvature of the whole tear meniscus as well as the tear meniscus of the nasal side(2,3,and 4 mm)aid in identifying the presence of dry eye and assessing its severity.CONCLUSION:This study contributes to the understanding of tear meniscus dynamics as potential markers for dry eye,utilizing an automated and non-invasive approach that has implications for clinical assessment.

Ocular surface microbiota in patients with varying degrees of dry eye severity

AIM:To elucidate the profiles of commensal bacteria on the ocular surfaces of patients with varying severity of dry eye(DE).METHODS:The single-center,prospective,case-control,observational study categorized all participants into three distinct groups:1)control group(n=61),2)mild DE group(n=56),and 3)moderate-to-severe DE group(n=82).Schirmer’s tear secretion strips were used,and the bacterial microbiota was analyzed using 16S ribosomal ribonucleic acid gene sequencing.RESULTS:The three groups had significant differences in alpha diversity:the control group had the highest richness(Chao1,Faith’s phylogenetic diversity),the mild DE group showed the highest diversity(Shannon,Simpson),and the moderate-to-severe DE group had the lowest of the above-mentioned indices.DE severity was positively correlated with a reduction in beta diversity of the microbial community,with the moderate-to-severe DE group exhibiting the lowest beta diversity.Linear discriminant analysis effect size presented distinct dominant taxa that significantly differed between each.Furthermore,the exacerbation of DE corresponded with the enrichment of certain pathogenic bacteria,as determined by random forest analysis.CONCLUSION:As DE severity worsens,microbial community diversity tends to decrease.DE development corresponds with changes in microbial constituents,primarily characterized by reduced microbial diversity and a more homogenous species composition.

Dry eye disease among patients infected with the SARSCoV-2 Omicron variant:a cross-sectional study

AIM:To investigate the incidence of dry eye disease(DED)and relevant risk factors among patients infected with the severe acute respiratory syndrome coronavirus 2(SARSCoV-2)Omicron variant.METHODS:This cross-sectional,observational analysis included 993 patients with corona virus disease 2019(COVID-19)treated at the National Exhibition and Convention Center(Shanghai)Fangcang Shelter Hospital,from April 10 to May 26,2022.Totally 944 uninfected control participants were recruited.All participants completed ocular surface disease index(OSDI)questionnaires,and DED symptoms were determined using OSDI scores.The demographic characteristics,length of hospital stay and in nasopharyngeal swabs were performed using questionnaires.SARS-CoV-2 Omicron variant infection was confirmed by nucleic acid-based detection in nasopharyngeal swabs using a 2019-nCoV nucleic acid detection kit.The risk factors for DED symptoms among patients with COVID-19 and control participants were determined by logistic regression analysis.RESULTS:Patients with COVID-19 showed a higher incidence of DED than controls(64.9%vs 55.1%,P<0.001).SARS-CoV-2 infection[odds ratios(ORs)(95%CI):1.271(1.038,1.556)],use of contact lenses[ORs(95%CI):9.350(3.676,23.783)],history of corneal refractive surgery[ORs(95%CI):2.047(1.494,2.804)],poor sleep quality[ORs(95%CI):2.657(2.029,3.480)],and video display terminal(VDT)use for more than 8h per day[ORs(95%CI):6.348(4.720,8.538)]were found to be risk factors for DED symptoms in patients with COVID-19 as well as controls.For patients with COVID-19,the length of hospital stay[ORs(95%CI):1.196(1.134,1.262)],use of contact lenses[ORs(95%CI):20.423(2.680,155.632)],history of corneal refractive surgery[ORs(95%CI):2.166(1.321,3.553)],poor sleep quality[ORs(95%CI):3.650(2.381,5.597)],and VDT use for more than 8h per day[ORs(95%CI):7.740(4.918,12.180)]were significant risk factors for DED symptoms.CONCLUSION:Patients with COVID-19 are more prone to develop symptomatic DED.SARS-CoV-2 infection and length of hospital stay are important risk factors for DED symptoms.

Randomized controlled trial on the efficacy and safety of autologous serum eye drops in dry eye syndrome

BACKGROUND Autologous serum eye drops(ASEDs),a novel treatment derived from blood serum,have emerged as a groundbreaking solution for managing dry eye syndrome(DES).These drops have shown significant promise in relieving the distressing symptoms of DES.This study aimed to evaluate the safety and effectiveness of ASEDs compared to traditional treatments,which often prove inadequate or result in unwanted side effects,particularly in individuals with moderate-to-severe DES.AIM To evaluate whether ASEDs are safer and more effective than conventional artificial tears in the treatment of moderate-to-severe DES.METHODS This multi-centered randomized controlled trial included 240 patients with moderate-to-severe DES from three ophthalmology clinics in China.They were randomly assigned to receive either ASEDs or artificial tears for 12 wk.The primary outcome was the change in the ocular surface disease index(OSDI)score,with secondary outcomes including tear break-up time(TBUT),Schirmer I test,corneal fluorescein staining(CFS),and conjunctival impression cytology(CIC).Statistics analysis was performed using an analysis of covariance with adjustments made for baseline values.RESULTS Our findings revealed that both ASEDs and artificial tears significantly improved the OSDI score,TBUT,Schirmer I test,CFS,and CIC from baseline to week 12.The ASEDs group showed significantly greater improvement in all these measures than the artificial tears group(all P values<0.05).The average difference in the OSDI score between the two cohorts was-10.3(95%confidence interval:-13.6 to-7.0),indicating a substantial improvement in the ASEDs group.The occurrence of adverse events was comparable between cohorts,with no reports of severe adverse events.CONCLUSION ASEDs are more effective and safer than artificial tears for mitigating symptoms of moderate-to-severe DES.ASEDs could be an alternative/supplementary therapy for patients with DES less responsive to traditional treatments.

Recent advance in natural plant products for treatment of dry eye disease

Dry eye disease(DED),a chronic multifactorial illness of the ocular surface with itching,burning,irritation,eye fatigue and ocular inflammation,may result in potential damage,such as cornea and conjunctiva,and even decreased vision.With the global prevalence of DED on the rise,it is crucial to find treatment options with minimal side effects.Natural plant products have shown promise in alleviating DED symptoms and may serve as a potential approach for its treatment.However,their application as instilled drugs is limited by solubility,stability and biological barriers.This review summarizes recent studies(published in the last 5 years)on natural plant products and their derivatives for the treatment of DED,focusing on efficacy,mechanism,drug delivery systems.Meanwhile,their shortcomings are also discussed.By exploring these aspects,we find polyphenol,flavonoid and others natural plant products can effectively improve or treat DED by different mechanisms,and suitable delivery system and structural modification can enhance their therapeutic effect,suggesting they are likely to become candidates for the treatment of DED.

A network pharmacology-based investigation of the mechanism of action of chrysanthemum in treating dry eye

Background:Dry eye is a chronic inflammatory disease of the ocular surface that is caused by multiple factors,characterized by pain,visual disturbance,and ocular damage.It is a common ophthalmic disease worldwide and a hot research field for scholars both domestically and internationally.This article employs network pharmacology methods to analyze the mechanism of Chrysanthemum in treating dry eye,which is a promising approach.Methods:The TCMSP(http://tcmspw.com/tcmsp.php)was used to screen for candidate active ingredient molecules of chrysanthemum with oral bioavailability≥30%and drug similarity to chrysanthemum≥0.18 as parameters.The active ingredients of chrysanthemum were searched using the“Related Targets”column in the TCMSP,followed by target prediction.Subsequently,Cytoscape 3.6.0 was employed to construct a compound-target network for chrysanthemum.The Online Mendelian Inheritance in Man and DisGeNET databases were used to identify pathogenic genes associated with dry eye.Furthermore,the STRING database was used to construct an interaction network and bar graph of intersecting target proteins in chrysanthemum to analyze protein interactions and core targets.To obtain key targets of active ingredients of chrysanthemum for treating dry eye,active ingredients targets of chrysanthemum and dry eye targets were intersected using Venny.Finally,a drug-active ingredient-key target-disease network was constructed.Gene Ontology functional annotation of key targets was performed using the WEBGESTALT database,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment was performed using the REACTOM database.Results:Eighty active ingredients of chrysanthemum corresponding to targets were obtained.Among active ingredients,508 predicted targets were identified,along with 4180 genes associated with dry eye and 45 key targets of chrysanthemum for treating dry eye.The functions of key targets primarily include regulation of gene expression,oxidative stress,immune response,apoptosis,proliferation,regulation of cellular inflammation-related factors,and angiogenesis.The primary pathways associated with key targets include interleukin signaling,metabolism,cytokine signaling in the immune system,immune system,and signal transduction.Conclusion:Chrysanthemum facilitates regulation through multiple molecules,targets,and pathways for treating dry eye,primarily inhibiting inflammation-related factors and pathways,thereby reducing inflammation of lacrimal gland tissue and improving dry eye.

Pro-inflammatory cytokines levels in tears and dry eye disease in Parkinson’s disease

Background:Neuroinflammation is an essential event in Parkinson’s disease(PD).Identifying affordable and less invasive biomarkers to make an early diagnosis and monitor therapeutic strategies should be a priority among researchers.The study’s objective was to measure tear levels of cytokines in subjects with PD and their association with motor features and the presence of dry eye symptoms.Methods:A total of 16 subjects with PD and 16 age-and sex-matched controls were included.Movement Disorders Society-Unified Parkinson’s Disease Rating Scale(MDS-UPDRS),Hoehn and Yahr(HY)stage scale,Montreal Cognitive Assessment(MoCA),tear break-up time(TBUT),blink rate(BR),Dry Eye Questionnaire 5(DEQ-5)were examined,and pro-inflammatory cytokines[interleukin(IL)-1β,IL-6,IL-8,IL-10,IL-12p70 and tumor necrosis factor-alpha(TNF-α)]were quantified in tears using the BD Cytometric Bead Array Human Inflammatory Cytokine Kit.Results:Higher tear TNF-αwere quantified in PD compared to controls(2.94±3.95 vs.0.33±0.49 pg/mL,P=0.008).According to DEQ-5,50.0%(n=8)of PD subjects and 12.5%(n=2)controls had dry eye disease(DED).No differences were found in cytokines concentrations between PD patients with DED compared to those without DED.IL-8 was associated with the HY stage,TBUT,DEQ-5,and a better MoCA score.A higher BR correlated moderately with a lower HY stage(r=−0.645,P=0.007),and DED patients have lower BR in PD(12.14±2.54 vs.9.0±2.06 blinks/minute,P=0.031).Conclusions:PD patients have higher levels of TNF-αin tears than age-and sex-matched HC.IL-8 in tears may be both involved in the severity of the disease and in the development of DED in PD.In addition,our findings suggest that as HY stage increases,indicating a more advanced stage,BR decreases,indicating greater motor impairment.Conversely,the presence of DED is associated with higher levels of bradykinesia in PD patients,suggesting a potential relationship between DED and motor impairment severity.