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.

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 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.

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.

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.

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.

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.

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.

Evaluation of patients with dry eye disease for conjunctival Chlamydia trachomatis and Ureaplasma urealyticum

AIM：To determine the possibility of the development of dry eye disease（DED） as a result of persistent infection with Chlamydia trachomatis and Ureaplasma urealyticum in the conjunctiva of patients.METHODS： This study was conducted on 58 patients of age range 20-50 y,diagnosed with DED confirmed by Schirmer I test and tear breakup time.The non-dry eye control group included 27 subjects of the same age.Ocular specimens were collected as conjunctival scrapings and swabs divided into three groups： the first used for bacterial culture,the second and third taken to detect Chlamydia trachomatis and Ureaplasma urealyticum by direct fluorescent antibody（DFA） assay and polymerase chain reaction（PCR） method. RESULTS： Chlamydia trachomatis was detected in 65.5% and 76% of DED patients by DFA and PCR methods respectively.Ureaplasma urealyticum was found in 44.8% of DED infected patients using the PCR method.Both organisms were identified in only 37.9% of DED patients found to be infected.Control subjects had a 22%detection rate of Chlamydia trachomatis by DFA assay versus a 7% detection rate by PCR; while Ureaplasma urealyticum was detected in 3.7% of the controls by PCR method.The conjunctival culture revealed that gram positive microorganisms represented 75% of isolates with coagulase negative Staphylococci the most common（50%） followed by Staphylococcus aureus（20%）,whereas gram negative microorganisms occurred in 25% of cases,isolating Moraxella spp.as the most frequent organism. CONCLUSION： Our results tend to point out that Chlamydia trachomatis and Ureaplasma urealyticum were detected in a moderate percentage of patients with DED,and could be a fair possibility for its development.PCR is more reliable in detecting Chlamydia trachomatis than DFA technique.The presence of isolated conjunctival bacterial microflora can be of some potential value.

Effect of topical 0.05% cyclosporine A on corneal endothelium in patients with dry eye disease

· AIM: To determine the effect of topical 0.05% cyclosporine A (CsA) on corneal endothelium in patients with dry eye disease. · METHODS: Observational, prospective, case series study. Fifty-five eyes of 29 consecutive patients (9 males and 20 females; median age: 66.8 years, interquartile range: 61 -73.2 years) with moderate -severe dry eye disease were evaluated. All patients were treated with topical 0.05% CsA ophthalmic emulsion twice a day in addition to lubricant eyedrops 5 times a day. The follow- up period was 12 months. Before treatment and at 3 and 12 months post -treatment central corneal specular microscopy was performed. The endothelial cell density (ECD), coefficient of variation of cell size (CoV), and percentage of hexagonal cells (Hex %) were analyzed. ·RESULTS: The median ECDs pre-treatment and at 3 and 12 months post-treatment were 2 352.5/mm 2 (inter- quartile range, 2 178 -2548.5), 2 364/mm 2 (interquartile range, 2 174.25 -2 657.5), and 2 366 cells/mm 2 (inter - quartile range, 2 174.75-2 539.75), respectively (P=0.927, one way ANOVA). The median CoVs pre-treatment and at 3 and 12 months post -treatment were 34.5 (interquartile range, 30 -37), 35 (interquartile range, 30 -38), and 34 (interquartile range, 30.75-38.25), respectively (P=0.7193, one way ANOVA). The median Hex % values pre - treatment and at 3 and 12 months post -treatment were 53 (interquartile range, 47 -58), 54 (interquartile range, 45.75 -59), and 50.5 (interquartile range, 45.75 -58), respectively (P=0.824, one way ANOVA). · CONCLUSION: Treatment of patients with dry eye disease for 12 months with topical 0.05% CsA does not seem to cause substantial changes on corneal endothelium.

Inflammation and dry eye disease——where are we?

The presence of inflammation in dry eye disease(DED)results in increased patient symptomatology,ocular surface damage and worsening tear dysfunction.It also affects the health of meibomian glands and their secretions which further aggravates ocular surface disease.This article reviews current knowledge regarding ocular surface inflammation in DED and explores the relationships between the vicious cycles of DED,inflammation and meibomian gland dysfunction(MGD).The clinical evaluation of eyes with such changes,markers that identify the presence of inflammation on the ocular surface and current treatment options are discussed.

Factors influencing subjective symptoms in dry eye disease

AIM: To retrospectively investigate the association between dry eye symptoms and clinical or in vivo confocal microscopy parameters in patients with dry eye disease(DED), and to compare these parameters between eyes with DED and normal subjects.METHODS: This retrospective, cross-sectional, controlled study comprised 25 consecutive patients with non-Sj?gren dry eye disease and age-and sex-matched 25 healthy subjects. Each patient underwent a complete examination of the ocular surface in the following order: tear osmolarity measurements, InflammaDry test, tear break-up time, corneal fluorescein staining, Schirmer I test, subjective symptoms questionnaire using the dry eye-related qualityof-life score(DEQS), and in vivo confocal microscopy analysis of the central cornea. Beck depression inventory(BDI) as depressive scale and history of medications and smoking were also evaluated. Stepwise multiple regression analysis was used to assess the factors affecting the DEQS.RESULTS: In univariate analysis, DEQS was associated with tear break-up time(ρ=-0.48, P=0.01), oral medications, such as hypotensive drug(ρ=0.56, P=0.004) and antidepressant(ρ=0.57, P=0.003), and BDI(ρ=0.61, P=0.001) in patients with DED. In multiple regression analysis, explanatory variables relevant to the DEQS were the anti-depressant medications(P=0.04, partial regression coefficient B=21.04) and BDI(P=0.02, B=0.76, adjusted R2=0.54) in these patients. CONCLUSION: Our study shows a significant association between depression and dry eye symptoms. It suggests that dry eye symptoms associate with higher depressive symptoms and its medications, although our patients were not followed longitudinally.

Prevalence and risk factors of dry eye disease in young and middle-aged office employee:a Xi’an Study

AIM:To estimate the prevalence of and risk factors for dry eye disease(DED)in young and middle-aged office employee in Xi’an.METHODS:This cross-sectional study of the prevalence of and risk factors for DED investigated 486 young and middle-aged Chinese office employee in Xi’an.DED symptoms and potential risk factors were assessed using the ocular surface disease index combined with a risk factors questionnaire,and tear function was evaluated using the tear film break-up time and Schirmer’s test.Possible risk factors for DED were estimated by binary Logistic regression analysis.RESULTS:DED was diagnosed in 100 females and 96 males,giving a prevalence of 40.3%[95%confidence interval(CI)=36.0%-44.7%].The multivariate binary Logistic regression model indicated that the possible risk factors for DED were being female(OR=1.592,95%CI=1.034-2.451,P=0.035),being aged≥40 y(OR=1.593,95%CI=1.034-2.454,P=0.035),using a VDT daily for>6 h(OR=1.990,95%CI=1.334-2.971,P=0.001),the presence of central air conditioning(OR=1.548,95%CI=1.053-2.276,P=0.026),and self-reported dryness of the mouth and nose(OR=1.589,95%CI=1.071-2.357,P=0.021).CONCLUSION:There is a high prevalence of clinically diagnosed DED in young and middle-aged video displayterminal(VDT)users.Interventions against the modifiable risk factors should be taken to prevent the occurrence and development of DED in this population.

Crosslinked hyaluronic acid with liposomes and crocin for management symptoms of dry eye disease caused by moderate meibomian gland dysfunction

AIM:To study the effect of uncrosslinked and crosslinked hyaluronic acid combined with other artificial tear components in patients with dry eye caused by moderate meibomian gland dysfunction.METHODS:Prospective,single-blind,contralateral eye study.Fifty eyes(25 patients)were analyzed.Eye selection for each tear type was random,and the eye drop formulations,0.4%uncrosslinked hyaluronic acid and 0.2%galactoxyloglucan(tear A)and 0.15%crosslinked hyaluronic acid,crocin,and liposomes(tear B)were used.The determined dosing schedule was three times a day for six weeks,and the study participants underwent a clinical examination before and 45 d after lubricant treatment.The Schirmer test,tear breakup time(TBUT)test,and Ocular Surface Disease Index(OSDI)questionnaire were applied before and after instillation period with both types of artificial tears.RESULTS:On the Schirmer test,a significant improvement was obtained with both tear A(P<0.01)and tear B(P<0.01).On the TBUT test,a significant improvement was obtained with tear A(P<0.01)and tear B(P<0.01).The OSDI score significantly decreased after instillation period with both artificial tear types(P<0.01).CONCLUSION:Uncrosslinked hyaluronic acid combined with other components,such as tamarind seed polysaccharide,and crosslinked hyaluronic acid combined with liposomes and crocin are effective for management symptoms of dry eye disease.

Clinical effectiveness of diquafosol ophthalmic solution 3%in Korean patients with dry eye disease:a multicenter prospective observational study

AIM:To investigate the effectiveness of diquafosol ophthalmic solution 3%administered in Korean patients with dry eye disease in real-world clinical settings.METHODS:Diquafosol was administered for 8 wk to 3 patient groups who received diquafosol as add-on therapy to existing medication(Add group,n=150);received diquafosol only(Monotherapy group,n=196);or discontinued part of their existing medication in favor of diquafosol(Switch group,n=11).Tear break-up time(TBUT),cornea and conjunctival staining based on National Eye Institute/Industry scoring scheme,subjective symptoms using the Ocular Surface Disease Index(OSDI)questionnaire,and meibum quality and expressibility were evaluated at baseline,week 4,and week 8.RESULTS:The mean TBUT increased(from 3.46,3.92,and 5.84 s,respectively,to 5.15,5.53,and 8.59 s,respectively)and corneal staining score decreased(from 2.23,2.24,and 3.09,respectively,to 0.85,0.97,and 1.64,respectively)in a time-dependent manner from baseline to week 8 in all three groups.Conjunctival staining score,OSDI questionnaire,and meibum quality and expressibility improved over time from baseline to week 8 in the Add and Monotherapy groups,but differences were not statistically significant in the Switch group.CONCLUSION:Diquafosol improves subjective symptoms and objective signs in patients treated with existing medicines combined with diquafosol and treated solely with diquafosol.Diquafosol can be used as an effective therapeutic agent for dry eye disease or additionally applied in patients who have insufficient response to existing medicines.

Gender differences in adolescent dry eye disease:a health problem in girls

AIM： To evaluate the signs and symptoms of dry eye disease（DED） in adolescents. METHODS： This was a cross-sectional, case-control study and outpatients aged 10 to 19y were recruited from six eye clinics of various practices and locations in Japan, and 253 non-DED subjects and 70 DED patients were enrolled. Participants were examined for DED-related signs. Patients were also interviewed to ascertain the presence or absence of six common DED-related symptoms： dryness, irritation, pain, eye fatigue, blurring, and photophobia. Main outcome measures were differences in signs and symptoms of dry eye disease between boys and girls.RESULTS： Of the 323 adolescents recruited, 70（21.7%） were diagnosed with DED. Significant differences between the non-DED and DED groups were found for short tear break-up time（BUT; ≤5s; P=0.000） and superficial punctate keratopathy（SPK; staining score ≥3; P=0.000）. Late adolescent girls reported fewer symptoms than late adolescent boys, although their DED-related signs were worse compared to other groups. The prevalence and severity of DED were similar in the Tokyo area compared with suburban and local areas but myopic errors were worse. CONCLUSION： We find that adolescents reported symptoms of DED similar to those found in adults, and the majority have short BUT-type DED. The prevalence and severity of DED in late adolescent girls is comparable with adults. Adolescents with DED are underserved and we believe that DED is a hidden but potentially serious health problem for this age group.

Effect of natural extract eye drops in dry eye disease rats

AIM:To investigate the therapeutic effect of natural extract eye drops containing bee venom,musk,and deer antlers in dry eye disease(DED)animal models.METHODS:Scopolamine-injected DED rats and lacrimal gland-excised rats were allocated into control,saline,and natural extract groups respectively and a normal group(lacrimal gland excision was not performed)in lacrimal gland-excised rats.After eye drop instillation 4 times a day for 5 d,corneal fluorescein staining(CFS)scores,tear MUC5AC levels,and tear lactic dehydrogenase(LDH)levels were measured.RESULTS:In scopolamine-injected rats,the natural extract-treated group had significantly lower CFS scores(1.7±0.5,4.7±1.4,3.8±1.9,P=0.006)and tear LDH levels(0.10±0.01,0.19±0.01,0.16±0.08 OD,P=0.014)but higher tear MUC5AC levels(12.9±3.7,7.9±2.0,9.7±3.6 ng/m L,P=0.041)compared with the control and saline-treated groups.There were no significant differences between the control and saline-treated groups.In lacrimal gland-excised rats,the natural extract-treated group also had lower CFS scores(4.3±1.2,11.5±2.3,9.0±1.9,P<0.001,P=0.001)and tear LDH levels(0.30±0.08,0.48±0.12,0.39±0.05 OD,P<0.05)but higher tear volume(4.3±0.9,1.9±0.7,2.8±1.1 mm,P=0.005,P=0.124)and tear MUC5 AC levels(8.2±2.0,2.9±1.2,5.4±2.2 ng/m L,P<0.001,P=0.047)compared with the control and saline-treated groups.There were no significant differences in the CFS scores,tear MUC5AC level,and tear LDH level between the normal and natural extracttreated groups.CONCLUSION:The natural extract consisting of bee venom,musk,and deer antlers may have effectiveness in DED treatment by restoring the damaged ocular surface,increasing tear volume,and recovering the tear mucin layer in DED rats.

Transgenic dry eye mouse models: powerful tools to study dry eye disease

Dry eye disease(DED) is one of the most common chronic multifactorial ocular surface diseases with high prevalence and complex pathogenesis. DED results in several ocular discomforts, vision fluctuation, and even potential damage of the ocular surface, bringing heavy burdens both on individuals and the society. The pathology of DED consists of tear film hyperosmolarity and immune responses on the ocular surface. Mice are widely used for developing models that simulate human DED features for investigating its pathogenesis and treatment. DED can be classified into aqueous-deficiency dry eye(ADDE) and evaporative dry eye(EDE). ADDE can be further divided into Sj?gren syndrome dry eye(SSDE) and non-Sj?gren syndrome dry eye(NSSDE). SSDE mouse models include natural strains, typified by non-obese diabetic(NOD) mice, and genetically engineered ones, like Aire-/-and Id3 knockout mice. Intrinsic EDE mainly refers to meibomian gland dysfunction(MGD). Eda-/-Tabby, Sod1-/-, Elovl1-/-are the most common transgenic MGD mouse models. Transgenic mouse models provide useful tools for studying the pathogenesis of DED and evaluating its novel therapies. This review compares the major transgenic dry eye mouse models and discusses their applications in DED research.

Systematic Review on the Epidemiology and Management of the Dry Eye Disease in Sub-Saharan Francophone Africa

Introduction: Dry Eye Disease (DED) is a multifactorial affection of the tears and the ocular surface. Its prevalence in the world varies between 7% and 33%. To the best of our knowledge, the prevalence of DED in Subsaharan Francophone African countries is not yet known. The objectives of this systematic review were to determine the prevalence of DED, to identify the main risk factors for DED, and to determine the diagnostic and therapeutic management of DED in Subsaharan Francophone African countries. Methodology: This is a systematic review of articles, dealing with DED, published in English or French language from 2010 to 2020. The following key words (Prevalence OR Incidence OR Proportion OR Rate OR Frequency OR Epidemiology OR Distribution) AND (Risk Factors OR Influences) AND (Symptoms or Questionnaire) AND (Clinical Signs OR Clinical Tests) AND (Dry Eye Disease OR Dry Eye Syndrome) AND (Pharmacological Treatment OR Non-pharmacological Treatment OR Management) AND (Benin OR Burkina Faso OR Burundi OR Cameroon OR Cap-Green OR Central African Republic OR Congo OR Congo (Democratic Republic of) OR Ivory Coast OR Gabon OR Guinea OR Guinea-Bissau OR Equatorial Guinea OR Mali OR Madagascar OR Mauritius (island) OR Niger OR Rwanda OR Sao Tome and Principe OR Senegal OR Seychelles OR Chad OR Togo) in French and English were searched on Pubmed, Chocrane database, Google scholar and ICTRP. Articles in English and French were selected from 2010 to 2020. Results: We selected 05 articles on the epidemiology and management of DED in sub-Saharan francophone Africa. The prevalence of DED in sub-Saharan francophone Africa in the articles ranged from 7.5% to 90.4%. DED affects more women than men. The risk factors found were: age over 50 years, diabetes, meibomian gland dysfunction, prolonged use of computers, and glaucomatous anti-glaucoma drugs. The Test of Breack Up Time (TBUT) was commonly used for the clinical diagnosis of dry eye disease in Sub-Saharan Francophone Africa. The therapeutic strategy for DED was not mentioned in any article. Conclusion: DED, a multifactorial and blinding eye disease, is insufficiently explored by eye health professionals in sub-Saharan Francophone Africa. The implementation of a systematic screening program and strategies for the treatment of dry eye disease in at-risk individuals would be beneficial for sub-Saharan Francophone African countries.

Topical biological agents targeting cytokines for the treatment of dry eye disease

Because inflammation plays a key role in the pathogenesis of dry eye disease and Sjogren's syndrome, topical anti-inflammatory agents such as corticosteroids and cyclosporine A have been used to treat inflammation of the ocular surface and lacrimal gland. Systemic biological agents that target specific immune molecules or cells such as tumor necrosis factor(TNF)-α, interferone-α, interleukin(IL)-1, IL-6, or B cells have been used in an attempt to treat Sjogren's syndrome. However, the efficacy of systemic biological agents, other than B-cell targeting agents, has not yet been confirmed in Sjogren's syndrome. Several studies have recently evaluated the efficacy of topical administration of biological agents targeting cytokines in the treatment of dry eye disease. Topical blockade of IL-1 by using IL-1 receptor antagonist could ameliorate clinical signs and inflammation of experimental dry eye. Using a mouse model of desiccating stress-induced dry eye, we have demonstrated that topical application of a TNF-α blocking agent, infliximab, could improve tear production and ocular surface irregularity, decrease inflammatory cytokines and Th-1 CD4+ cells on the ocular surface, and increase gobletcell density in the conjunctiva. Although controversy still remains, the use of topical biological agents targeting inflammatory cytokines may be a promising therapy for human dry eye disease.