The Changes Of Ocular Surface Tear Film And Cytokines In Diabetic Patients With Dry Eye

ObjectiveDry eye is a common cause of ocular discomfort in diabetic patients.Due to the Complexity of the pathogenic factors of dry eye in diabetes,comprehensive analysis for etiology and pathogenesis of ocular surface disorders,finding targets for treatment,and in order to early intervention,is the important solution to diabetic ocular dysfunction so far.The objects of this study were the patients with diabetes in Tianjin,and they had been given a series of questionnaire and clinical examination associated with dry eye.Furthermore,this study explored the effect of diabetes on ocular surface,and analyzed the changes of cytokines in tear.Methods1.A total of 314 patients with type 2 diabetes were recruited from one of the hospitals in Tianjin.The general material data,ocular symptoms and clinical signs were collected.These patients underwent anterior segment with slit lamp examination,tear break-up time(TBUT),superficial punctuate keratopathy(SPK) scoring,Schirmer I test and dilated fundus examination.According to the data with diabetic patients,the impact factors of dry eye in diabetes were discussed.2.Ninety-one patients with diabetes and 51 healthy controls were recruited from Tianjin medical university,and the diabetics were divided into 3 subgroups according to the duration of diabetes,including duration<10 y group,10~20 y group,and≥21 y group.All subjects underwent clinical ocular examinations,including lipid layer thickness(LLT),blinking rate,tear meniscus height(TMH),non-invasive tear film break-up time(NI-BUT),meibography,SPK scoring,corneal sensitivity,and Schirmer I test.They were also evaluated using standard patient evaluation of eye dryness(SPEED)questionnaire.3.Sixty patients with diabetic course of more than 10 years and 60 healthy controls were recruited from Tianjin medical university.According to the diagnosis of dry eye,all subjects were divided in to 4 groups,including diabetes with dry eye group,diabetes group,dry eye group,and controls.Firstly,tear samples were collected and quantitatively detected by Human Dry Eye Disease Array Q1 (QAH-DED-1),then we picked up three cytokines,including EGF,IL-1RA,and MIP-1d,to measure the concentration in tears using ELISA in order to find the changes of these cytokines in dry eye,further to seek the indexes could evaluate the disease.Results1.The prevalence of dry eye in the groups of female(c~2=17.921,P=0.000)and poor control in blood glucose(c~2=5.858,P=0.016)were significantly increased.There was significant difference in the incidence of dry eye among the groups of diabetic course(c~2=17.968,P=0.001),treatment(c~2=8.289,P=0.016)and diabetic complications(c~2=17.278,P=0.000).2.The SPEED score(Z=-3.600,P=0.000),meiboscore(t=-4.003,P=0.000),SPK score(Z=-2.463,P=0.014),LLT values(t=-2.018,P=0.045),Schirmer I test values(Z=-1.991,P=0.046),and corneal sensitivity(t=-4.100,P=0.000) significantly differed between the diabetic and control groups.The SPEED score (H=16.630,P=0.001),Schirmer I test result(H=14.164,P=0.003),corneal sensitivity(F=11.344,P=0.000),meiboscore(F=4.950,P=0.002),and blink rate (H=10.232,P=0.017)significantly differed among the 3 diabetic subgroups and control group.In the diabetic patients,SPEED score correlated with SPK score (r=0.300,P=0.000),Blink rate(r=0.146,P=0.050),TMH(r=-0.151,P=0.042),and LLT values(r=-0.286,P=0.000);NI-BUT with TMH(r=0.167,P=0.024),LLT values(r=0.160,P=0.031),and blinking rate(r=-0.193,P=0.009);TMH with SPK score(r=-0.165,P=0.026).There were also correlations between the Schirmer I test result and SPK score(r=-0.195,P=0.008),and between corneal sensitivity and meiboscore in the patients with diabetes(r=0.153,P=0.040).Importantly,Schirmer I test result(r=-0.268,P=0.000),corneal sensitivity (r=-0.336,P=0.000),and SPEED score(r=-0.171,P=0.021)negatively correlated with the duration of diabetes.3.There was a significant difference between diabetes with dry eye group and diabetes group(t=-2.155,P=0.045),diabetes with dry eye group and controls (t=-3.056,P=0.007),as well as dry eye group and controls(t=-2.215,P=0.040)in detecting EGF concentration in tears using ELISA.There was a significant difference between diabetes with dry eye group and diabetes group(t=4.556, P=0.000),diabetes with dry eye group and controls(t=-2.961,P=0.011),as well as dry eye group and controls(t=-2.215,P=0.040)in detecting IL-1RA concentration in tears using ELISA.There was a significantly difference between diabetes with dry eye group and diabetes group(t=4.556,P=0.000)in detecting MIP-1d concentration in tears using ELISA.Conclusion1.Sex,HbAlc,course,methods of treatment,DR,and surgery all are the influence factors in diabetic patients with dry eye.The dry eye morbidity in patients with diabetes is higher in women,worse control of HbAlc,course of>10 year,treatmentof oral medications,fundus with PDR and post fundus operation.2.The trends of ocular surface disorders in patients with diabetes vary along the course of diabetes,and the various ocular surface parameters interact with each other.Furthermore,schirmer I test result,corneal sensitivity,and SPEED score correlated with the duration of diabetes.3.The content of cytokines in tears may vary along the development of eye disease,and interact with each other in the process,thus affecting the state of disease.EGF,IL-1RA,and mip-1d are expected to be crucial indicators of early diagnosis and efficacy evaluation of treatment for dry eye in diabetes.