Meibomian glands segmentation in infrared images with limited annotation

●AIM:To investigate a pioneering framework for the segmentation of meibomian glands(MGs),using limited annotations to reduce the workload on ophthalmologists and enhance the efficiency of clinical diagnosis.●METHODS:Totally 203 infrared meibomian images from 138 patients with dry eye disease,accompanied by corresponding annotations,were gathered for the study.A rectified scribble-supervised gland segmentation(RSSGS)model,incorporating temporal ensemble prediction,uncertainty estimation,and a transformation equivariance constraint,was introduced to address constraints imposed by limited supervision information inherent in scribble annotations.The viability and efficacy of the proposed model were assessed based on accuracy,intersection over union(IoU),and dice coefficient.●RESULTS:Using manual labels as the gold standard,RSSGS demonstrated outcomes with an accuracy of 93.54%,a dice coefficient of 78.02%,and an IoU of 64.18%.Notably,these performance metrics exceed the current weakly supervised state-of-the-art methods by 0.76%,2.06%,and 2.69%,respectively.Furthermore,despite achieving a substantial 80%reduction in annotation costs,it only lags behind fully annotated methods by 0.72%,1.51%,and 2.04%.●CONCLUSION:An innovative automatic segmentation model is developed for MGs in infrared eyelid images,using scribble annotation for training.This model maintains an exceptionally high level of segmentation accuracy while substantially reducing training costs.It holds substantial utility for calculating clinical parameters,thereby greatly enhancing the diagnostic efficiency of ophthalmologists in evaluating meibomian gland dysfunction.

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.

Standardization of meibomian gland dysfunction in an Egyptian population sample using a non-contact meibography technique

AIM:To develop normative data for meibomian gland dysfunction(MGD)parameters,using non-contact meibography technique of Sirius Costruzione Strumenti Oftalmici(CSO)machine,in an Egyptian population sample.METHODS:Observational,cross-sectional,analytic study,in which 104 Egyptian volunteers were included.Both upper lids were examined,using“Sirius CSO”machine.Each eyelid was given a degree of meibomian gland loss(MGL),which was calculated by the software of the machine.RESULTS:Mean percentage MGL in right upper lid was of 30.9%±12.6%,and that of left upper lid was 32.6%±11.8%.Thirty-four volunteers(32.7%)had first-degree MGL in their right upper lid,and 67.3%had second-degree loss.One volunteer(1%)had zero-degree MGL in left upper lid,28(26.9%)had first-degree loss,and 75(72.1%)had second-degree loss.Degree of MGL in right upper eyelid was not related to age,but degree of MGL in left upper eyelid increased with age.There was statistically significant difference between both genders for degree of MGL in right eye(P=0.036)and in left eye(P=0.027).CONCLUSION:Noncontact meibography is a useful non-invasive tool for diagnosing MGL.MGL is diagnosed in 100%of apparently normal individuals;26.9%-32.7%of which have first-degree MGL,and 67.3%-72.1%have second-degree MGL.

The ILux^(®) compared to the mechanical meibomian gland expression for the treatment of moderate and severe meibomian gland dysfunction

AIM:To compare the safety and effectiveness of eyelid treatment with the ILux®-MGD Treatment System in one session versus five sessions of mechanical meibomian gland expression(MMGE)in patients with moderate to severe meibomian gland dysfunction(MGD).METHODS:A prospective,randomized,open-label,and controlled clinical trial that compared one session of the ILux®MGD Treatment System versus five sessions of MMGE in both eyes of 130 patients aged≥18y with Ocular Surface Disease Index(OSDI)scores≥13,total meibomian gland scores(MGS)of<15 in the lower eyelid of each eye,and non-invasive tear break-up time(NI-TBUT)<10s,who were randomized 1:1 to ILux®or MMGE.RESULTS:The mean age was 58±17.49y.Baseline total MGS scores in both treatment groups were comparable.During follow-up,there were significant differences in total MGS and per sector with P<0.001.Multivariate analysis was performed using generalized estimating equations corresponding to the generalized linear model for repeated means to determine the treatment relationship with total MGS,NIBUT,and OSDI.There was a significant difference between ILux®and MMGE(P<0.001)at follow-up from the first to the twelfth month in MGS,NI-BUT,and OSDI scores.No adverse events were reported.CONCLUSION:ILux®treatment compared to MMGE significantly improves symptoms and signs in patients with moderate to severe MGD for one year without adverse events.

Alkali burn injury model of meibomian gland dysfunction in mice

AIM:To establish a stable,short-time,low-cost and reliable murine model of meibomian gland dysfunction(MGD).METHODS:A filter paper sheet soaked in 1.0 mol/L sodium hydroxide(NaOH)solution was used to touch the eyelid margin of C57BL/6J mice for 10s to establish the model.The other eye was left untreated as a control group.Eyelid margin morphological changes and the meibomian glands(MGs)were observed by slit lamp microscopy on days 5 and 10 post-burn.Hematoxylin-eosin(HE)staining and Oil red O staining were adopted in detecting the changes in MGs morphology and lipid deposition.Real-time polymerase chain reaction,Western blot,immunofluorescence staining and immunohistochemical staining were used to detect interleukin(IL)-6,IL-1β,IL-18,tumor necroses factor(TNF)-α,interferon(IFN)-γ,nicotinamide adenine dinucleotide phosphate(NADPH)oxidase 4(NOX4),3-nitroturosine(3-NT),4-hydroxynonenal(4-HNE)and cytokeratin 10(K10)expression changes in MGs.RESULTS:MGs showed plugging of orifice,glandular deficiency,abnormal acinar morphology,ductal dilatation,and lipid deposition after alkali burn.The expressions of IL-6,IL-18,IL-1β,IFN-γ,and TNF-αindicators of inflammation and oxidative stress in MGs tissues were significantly increased.Abnormal keratinization increased in the MG duct.CONCLUSION:A murine model of MGD is established by alkali burn of the eyelid margin that matches the clinical presentation of MGD providing a stable,short-time,lowcost,and reliable MGD model.The new method suggests efficient avenues for future research.

Bilateral meibomian gland morphological alterations in unilateral herpes simplex keratitis based on artificial intelligence analysis

AIM:To explore whether unilateral herpes simplex keratitis(HSK)can cause morphological changes of bilateral meibomian glands(MGs)based on artificial intelligence(AI)analytical system.METHODS:In the retrospective study,29 patients with unilateral HSK and 29 participants matched in terms of age and sex were included as control group.Meibographic images of the upper eyelid using Keratograph 5M and assessed ocular surface parameters including tear meniscus height and tear break-up time.MG density and vagueness values were automatically analyzed and calculated using an AI analytical system.We compared the differences between the affected and the contralateral unaffected eyes in HSK patients,and the normal control eyes.We employed either the paired t-test or the Wilcoxon signed-rank test to compare significant difference between the affected and unaffected eyes in HSK patients or between the HSK group and control group.RESULTS:The MG density was 0.19±0.09 in the HSKaffected eye and 0.18±0.07 in contralateral unaffected eye,which had no significant difference(P=0.616).The MG density between the affected eye with HSK and the normal control group was statistically significant(P=0.028).There was a significant difference in MG density between the contralateral unaffected eye and the normal control group(P=0.012).However,no significant difference in vagueness value was observed between the eye with HSK and the control group or between HSK eye and contralateral eye.CONCLUSION:The MG density between the HSKaffected eye and the contralateral unaffected eye don’t significantly differ,whereas there is a significant decrease in the HSK group compared to that of the normal participants.Unilateral HSV keratitis may suffer from bilateral changes of MG morphology indicating bilateral dry eye.Therefore,the fellow eye of patients with unilateral HSK should be considered a potential case of MG dysfunction,necessitating early treatment for bilateral dry eye in the clinic.

Efficacy of indirect intense pulsed light irradiation on meibomian gland dysfunction: a randomized controlled study

AIM:To investigate the efficacy and mechanisms of indirect intense pulsed light(IPL)irradiation on meibomian gland dysfunction(MGD).METHODS:A total of 60 MGD patients was included in this prospective randomized controlled trial.Patients were randomly assigned 1:1 into two groups(3-mm group and 10-mm group)in which IPL was applied at distances from the lower eyelid margin of 3 and 10 mm,respectively.Both groups received three times treatment with 3-week interval.Meibomian gland yield secretion score(MGYSS),standard patient evaluation of eye dryness(SPEED)questionnaire,tear break-up time(TBUT),corneal fluorescein staining(CFS),and in vivo confocal microscopy were performed at baseline and after every treatment.RESULTS:After three IPL treatments,both groups had significant improvement in MGYSS(both P<0.05).The noninferiority test showed that improvement in 10-mm group was not inferior to that in 3-mm group(P<0.001).In both groups,temporal regions of both upper and lower eyelids showed significant improvement in MGYSS.Scores of SPEED questionnaire in both groups declined significantly(both P<0.001)and changes of SPEED had no difference between two groups(P=0.57).Density of central corneal subepithelial nerves and TBUTs showed no statistically significant changes.The 3-mm group had improvement on corneal fluorescein staining(P=0.048)and meibomian gland morphology(acini wall thickness P=0.003,hyperreflective points P=0.024)while the 10-mm group had not.CONCLUSION:The efficacy of IPL indirect irradiation in improving meibomian gland secretion and alleviating dry eye symptoms remains unchanged with increase in treatment distance.IPL may primarily act on the functional improvement of the meibomian glands and corneal nerves.

Research Progress of LipiFlow Therapy for Meibomian Gland Dysfunction

Meibomian gland dysfunction(MGD)is a common ocular surface disease,and the pathogenesis of MGD is closely related to the alteration of meibomian gland morphology and(or)function.At present,the treatment strategy for MGD consists of physical therapy,artificial lubricants,topical and systemic antibiotics and antiinflammatory agents,topical steroids andΩ-3 dietary supplementation.Recently,the thermal pulsation system(LipiFlow)has been used clinically,which allows heat to be applied to the palpebral surfaces of the upper and lower eyelids directly over the meibomian glands,while simultaneously applying pulsatile pressure to the outer eyelid surfaces.Due to its specific design,the cornea and eyeball can successfully avoid the potential damage from overheating and improper expression,which will greatly improve the safety during the clinical application and patients'compliance.Studies have showed that the effectiveness of LipiFlow when treating MGD is at least as well as twice-daily lid warming and massage for 3 months,which displays a broad application prospect.At present,the application of LipiFlow in China has not been fully developed,and only some hospitals have experimental applications.This paper summarizes the research progress of LipiFlow treatment in MGD.

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.

Retinal microvascular and microstructural alterations in the diagnosis of meibomian gland dysfunction in severely obese population:a new approach

AIM:To study retinal microvascular and microstructural alterations in meibomian gland dysfunction(MGD)in severely obese population using optical coherence tomography angiography(OCTA).METHODS:Twelve MGD patients with severely obese population(PAT group;24 eyes)and 12 healthy controls(HC group;24 eyes)were recruited.OCTA images were segmented into five[superior(S),nasal(N),inferior(I),temporal(T),and central foveal(C)]or nine[inner superior(IS),outer superior(OS),inner nasal(IN),outer nasal(ON),inner inferior(II),outer inferior(OI),inner temporal(IT),outer temporal(OT),and C]subregions.The superficial vessel density(SVD),retinal thickness(RT),foveal avascular zone(FAZ)parameters,and retinal volume were measured.RESULTS:Visual acuity was significantly different between two groups(0.8±0.17 in PAT group vs 0.2±0.06 in HC group).SVD was significantly lower in PATs in N,T,OS,IN,OT,and ON.The area under the receiver operating characteristic curve(AUC)for T was 0.961[95% confidence interval(CI):0.908 to 1.000],for OS was 0.962(95%CI:0.915 to 1.000).RT was significantly lower in PATs in IS,OS,OI,OT,ON,IT,IN,and II.AUC for OT was 0.935(95%CI:0.870 to 0.999),for IS was 0.915(95%CI:0.838 to 0.992).Angiography results showed significantly lower area and perimeter of FAZ,SVD of the inner retina and both retinal volume and the average volume thickness in the PAT group.CONCLUSION:Vision may be affected in patients with MGD due to changes in retinal microvessels and microstructures.These changes detected by OCTA may be a potential marker for diagnosing MGD in severe obesity.

Activities of autonomic neurotransmitters in meibomian gland tissues are associated with menopausal dry eye

The secretory activities of meibomian glands are regulated by the autonomic nervous system, The change in density and activity of autonomic nerves in meibomian glands during menopause play an important role in the pathogenesis of dry eye. In view of this, we established a dry eye rat model by removing the bilateral ovaries. We used neuropeptide Y and vasoactive intestinal polypeptide as markers of autonomic neurotransmitters. Our results showed that the concentration of estradiol in serum significantly decreased, the density of neuropeptide Y immunoreactivity in nerve fibers significantly increased, the density of vasoactive intestinal polypeptide immunoreactivity in nerve fibers significantly decreased, and the ratio of vasoactive intestinal polypeptide/neuropeptide Y positive staining significantly decreased. These results suggest that a decrease in ovary activity may lead to autonomic nervous system dysfunction, thereby affecting the secretory activity of the meibomian gland, which participates in sexual hormone imbalance-induced dry eye.

Changes of meibomian glands in patients with type 2diabetes mellitus

AIM： To investigate the morphological changes of meibomian glands in patients with type 2 diabetes mellitus （DM）.METHODS： Of 118 eyes （118 patients） with type 2 DM （DM group） and 100 eyes of 100 control subjects （control group） were enrolled. After completing an ocular surface disease index （OSDI） questionnaire, the non-invasive tear film break-up time （NI-BUT） and the structure of the meibomian glands （MGs, meibography） were assessed by the Keratograph 5M system. Partial or complete loss of MG was scored for each eyelid from grade 0 （no loss） to grade 3 （lost area was 〉2/3 of the total MG area）, which were also examined by laser scanning confocal microscopy （LSCM）. The primary outcomes were meibomian gland acinar unit density （MGAUD）, meibomian gland acinar longest diameter （MGALD） and meibomian gland acinar shortest diameter （MGASD）.RESULTS： Compared with control group, the OSDI was significantly higher in DM group （Z=-5.916; P〈0.001）, while the NI-BUT was significantly lower （Z=-7.765; P〈0.001）. Keratograph showed that there were more MGs dropout in DM group than that in control group. The meiboscore was significantly higher in DM group compared with control group （Z=-3.937; P〈0.001）. LSCM revealed that there were cytological alterations of MGs in DM group compared with control group, which included enlargement of MG acinar units and decreased in density of MG acinar units. Specifically, there were lower MGAUD, larger MGALD and MGASD in DM group than control group （Z=-10.120, -9.4442, -7.771; P〈0.001）.CONCLUSION： Compared with the normal control participants, the patients with type 2 DM had more unstable tear films and severe symptoms of dry eye. Using Keratograph 5M system and LSCM, we found that the patients with type 2 DM had more significant morphological and cytological changes and dysfunction in MGs.

Androgen and meibomian gland dysfunction:from basic molecular biology to clinical applications

Meibomian gland,the largest sebaceous gland of the body,is responsible for the biosynthesis of lipid layer of the tear film to prevent excessive evaporation.The loss of normal functions of meibomian gland,known as meibomian gland dysfunction(MGD),is a chronic disease and is the leading cause of dry eye symptoms in the clinics.Studies have found sex hormones,especially androgen,play vital roles in the regulation of the functions of meibomian gland.Recently,androgen has also been preliminarily applied in clinics for the treatment of MGD and showed promising results,especially in people with endogenous androgen deficiency.This review summarized the mechanisms of the function of androgen on meibomian gland based on molecular,animal,and clinical studies,and proposed evidence-based views about its potential applications for the treatment of MGD.

Effects of dietary high dose DHA omega-3 supplement in dry eye with meibomian gland dysfunction

AIM:To evaluate the clinical efficacy of dietary supplement of high dose DHA omega-3 in dry eye with meibomian gland dysfunction(MGD).METHODS:Prospective randomized double-masked,placebo-controlled clinical trial was conducted in mild to moderate dry eye patients with MGD.Patients have no history of taking any dietary omega-3 supplements before 3 mo.Patients were divided into two groups:24 patients in the omega-3 group and 26 patients in the placebo group.The omega-3 group received two capsules of Easyeye Dry?,total containing 600 mg of EPA and 1640 mg of DHA,while the placebo group received two capsules containing 3000 mg of olive oil.All patients take two pills once a day.The examination of MGD scores,tear break-up time(TBUT),corneal staining test(NEI),strip meniscometry(SM tube),and ocular surface disease index(OSDI)scores were performed at baseline,after 4 and 8 wk.RESULTS:A total of 50 patients were included.There were no differences in baseline characteristics between the two groups,such as age,sex,and other ocular examination findings.The TBUT,NEI,and OSDI scores significantly improved after 4 and 8 wk in both groups.While after 8 wk TBUT(6.00±1.62 s vs 5.08±1.28 s,P=0.034)and MGD score(7.2±1.8 vs 8.1±2.6,P=0.033)in the omega-3 group was more significantly improved than that of the placebo group.CONCLUSION:Dry eye with the MGD patient,a high dose of DHA omega-3 dietary supplement can improve TBUT and MGD score after 8 wk,effective in stabilizing the tear film.

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.

Comparison of the meibomian gland dysfunction in patients with chronic ocular graft-versus-host disease and Sjogren's syndrome

AIM: To investigate the abnormalities in the meibomian gland in patients with dry eye disease(DED) associated with chronic ocular graft-versus-host disease(coGVHD) in comparison with Sj?gren's syndrome(SS), a major form of aqueous deficient DED and meibomian gland dysfunction(MGD), a common cause of evaporative DED.METHODS: A total 135 eyes of 135 subjects included in this study: patients with DED associated with coGVHD(n=30), patients with SS(n=35), patients with MGD(n=35), and normal controls(n=35). All participants completed the Ocular Surface Disease Index(OSDI) questionnaire, ocular surface examination [Schirmer test, tear film breakup time(TFBUT), and ocular surface staining], and meibomian gland assessment [meiboscore(gland dropout detected on meibography using infrared camera of the Keratograph 5 M), meibum expressibility score(MES), meibum quality score(MQS), lid margin abnormality]. In addition, correlations of meibomian gland characteristics with ocular surface parameters as well as disease severity score were investigated in coGVHD group.RESULTS: The coGVHD group showed significantly higher meiboscore, MES, and MQS than the other 3 groups(all P<0.05). In the coGVHD group, parameters of meibomian gland showed a significant correlation each other and those of ocular surface. The correlation between meibomian gland parameters and severity score of co GVHD was also established(meiboscore, r=0.62; MES, r=0.47; MQS, r=0.47; lid margin abnormality score, r=0.55; all P<0.05).CONCLUSION: Patients with DED associated with co GVHD show poorer gland morphology and worse glandfunction than other types of DED. In addition, meibomian gland damage is not only associated with ocular surface damage but also disease severity of coGVHD.

Evaluation of a rat meibomian gland dysfunction model induced by closure of meibomian gland orifices

AIM： To find a stable, inexpensive, and reliable method to produce a rat meibomian gland dysfunction（MGD） model. METHODS： We inserted slim guidewires into the meibomian gland orifices of twelve Brown Norway rats and fulgurized every guidewire to destroy part of the meibomian gland. We then observed the morphological changes in the eyelid margin, and compared the data of tear breakup time（TBUT）, Schirmer I test, and the corneal fluorescence staining scores at different times（1, 2, 4, and 6 wk）. We observed pathological changes of the cornea, conjunctiva and meibomian gland, and we used real-time polymerase chain reaction to analyze epithelial growth factor（EGF）, interleukin-6（IL-6）, IL-8, tumor necrosis factor-α（TNF-α）, and Ki67. RESULTS： In the fourth week, compared with the control group, the TBUT of the model group began to decreased（P〈0.05）. The tear secretion remained stable（P〉0.05）. The corneal dots were significantly increased in the fourth week when the fusion stain began to appear（P〈0.05）. In the fourth week, partial meibomian gland openings had hoary secretions blocked, orifices were expanded, and there was a partial convex deformation. In the sixth week, the tissue section showed that the number of conjunctival goblet cells was decreased, epithelial cells were irregular, the epithelium was detached and rough, and meibomian glands were lost. The expressions of EGF, IL-6, IL-8, and TNF-α in corneal, conjunctival, and meibomian tissues were highly increased（P〈0.05）, but no statistical difference was found in the expression of Ki67 in corneal and conjunctival tissues（P〉0.05）. CONCLUSION： The MGD rat model, produced via electrocauterization of meibomian gland orifices, matched clinical manifestations and cytokine levels. Our research provides a new method of achieving an MGD animal model.

Clinical efficacy of combined topical 0.05%cyclosporine A and 0.1%sodium hyaluronate in the dry eyes with meibomian gland dysfunction

AIM： To investigate the efficacy of combined topical 0.05% cyclosporine A（CsA; Restasis~？, Allergan pharmaceuticals, USA） and 0.1% sodium hyaluronate treatment in dry eyes with meibomian gland dysfunction（MGD）.METHODS： In a retrospective analysis, 53 patients（106 eyes） with MGD were enrolled and performed lid warm massage for 10 min daily and be instilled preservative free sodium hyaluronate 0.1% eye drops 4 times daily. Patients were divided into subjects treated with topical 0.05% CsA and preservative free sodium hyaluronate vehicle（experimental group, n=74 eyes） and subjects treated with the preservative free sodium hyaluronate vehicle（control group, n=32 eyes）. They were evaluated at baseline and 1, 2, and 3 mo for subjective symptoms and objective signs including tear film break-up time（t BUT）, Schirmer test, corneal staining（CS） score, lid margin telangiectasia（LMT）, meibomian gland secretion（MGS）, and conjunctival injection（CI）.RESULTS： In the short-term treatment, the experimental group showed a statistically significant improvement in the ocular surface disease index（OSDI; P〈0.001）, tBUT（P=0.004）, Schirmer test score（P=0.008） and LMT（P=0.021） by repeated measure ANOVA. Additionally, mean changes from baseline in OSDI（P〈0.001）, tBUT（P=0.001）, Schirmer test score（P=0.029）, CS score（P=0.047）, LMT（P=0.002）, CI（P=0.030） were improved better in the experimental group than in the control group at 3 mo. However, there was no significant difference between the two groups in MGS（P=0.67）.CONCLUSION： In dry eyes with MGD, 0.05% CsA improves the tear film stability as well as subjective ocular discomfort, and is effective in controlling lid margin inflammation.

The association between demodex infestation and ocular surface manifestations in meibomian gland dysfunction

AIM： To investigate the association between ocular demodex folliculorum infestation and ocular surface manifestations in meibomian gland dysfunction（MGD）.METHODS： Eight-six patients with MGD were enrolled. All enrolled subjects were tested in the following sequence： ocular surface disease index（OSDI）, slit-lamp biomicroscope examination, corneal surface regularity index（SRI） and surface asymmetry index（SAI）, tear fluid collection, fluorescein tear film break-up time（F-BUT）, corneal fluorescein staining（CFS）, Schirmer I test（SIT） and demodex folliculorum counting. Tear matrix metalloproteinase（MMP）-9 activity was assessed using MMP-9 activity assay kit.RESULTS： Among 86 MGD patients, 40 were positive for demodex. The ocular demodex-positive group showed significantly increased scores of OSDI（25.96±13.74 vs 18.07±11.55, P=0.01）, lid margin abnormality（2.38±0.87 vs 1.98±0.91, P=0.04） and CFS（1.28±2.00 vs 0.94±1.36, P=0.01） compared to the ocular demodex-free group. The tear MMP-9 activity was higher in the ocular demodex-positive group（102.9±32.4 ng/mL） than the ocular demodex-free group（46.2±19.2 ng/mL, P=0.03）. There was no significant difference in meibum quality and expressibility, SRI, SAI, F-BUT and SIT between the two groups（P〉0.05 for each）. No significant correlation was noted between the number of demodex and ocular surface parameters in demodexpositive MGD group（P〉0.05 for each）.CONCLUSION： Ocular demodex folliculorum infestation may be associated with ocular discomfort and ocular surface damage in MGD.

Clinical efficacy of 0.05%cyclosporine nano-emulsion in the treatment of dry eye syndrome associated with meibomian gland dysfunction

AIM:To evaluate the clinical efficacy of topical 0.05%cyclosporine nano-emulsion in the treatment of dry eye syndrome(DES)with meibomian gland dysfunction(MGD).METHODS:This prospective study included 64 patients with DES and MGD who were randomly assigned to three groups:Group 1(n=24,conventional cyclosporine),Group 2(n=21,nano-emulsion cyclosporine),and Group 3(n=19,control).Lid margin telangiectasia(LMT),meibomian gland secretion(MGS),conjunctival injection(CI),corneal staining(CS),tear break-up time(TBUT),Schirmer test I(STI),Ocular Surface Disease Index(OSDI),and lipid layer thickness(LLT)was evaluated at 4,8,and 12wk of treatment.RESULTS:In Group 3(control),LMT,CS,and CI improved after 8wk,MGS,TBUT after 12wk of treatment.In Group 1(conventional cyclosporine),LMT,MGS,and TBUT improved significantly after 4wk,whereas CS,CI,STI,and LLT improved significantly after 8wk,and OSDI at 12wk.In Group 2(nano-cyclosporine),LMT,MGS,CS,CI,TBUT,and OSDI significantly improved after 4wk,and STI after 8wk.Especially,LLT was significantly higher than other groups after 4wk.CONCLUSION:Cyclosporine and nano-cyclosporine shows significant improvement in DES with MGD than the control group.In contrast,the nano-cyclosporine group shows more statistically improved CI and CS at 4wk,especially LLT at 4,8,and 12wk compared to the conventional cyclosporine group.