Establishment Of A Risk Prediction Model And Intervention For Diabetic Retinopathy

Purpose To elucidate the risk factors of diabetic retinopathy in type 2 diabetes patients,establish and validate a risk prediction model for diabetic retinopathy,and provide scientific reference for the prevention and screening of diabetic retinopathy.To investigate the changes of vitreous protein profiles in advanced proliferative diabetic retinopathy patients with preoperative intravitreal ranibizumab injection,and to explore the mechanisms that ranibizumab may participate in.Methods(1)This is a retrospective analysis of 4291 type 2 diabetes patients treated at the ophthalmology and endocrinology department of our hospital from January 2008 to December 2016.Gender,age,duration of diabetes,height,weight,waist circumference,systolic blood pressure and diastolic pressure were collected.Laboratory data were also collected,including creatinine,urea,uric acid,blood electrolytes(potassium,sodium,chlorine,calcium,magnesium),fasting blood glucose,OGTT 2h blood glucose,fasting insulin,OGTT 2h insulin,fasting C peptide,OGTT 2h C peptide,glycated hemoglobin,glycated albumin,total cholesterol,triglycerides,high density lipoprotein,low density lipoprotein,24 h urine protein quantification.All patients were randomly divided into a model group(3861 cases)and a validation group(430 cases)at a ratio of 9:1.All patients were divided into non-diabetic retinopathy(NDR)and diabetic retinopathy(DR)according to the 2002 international clinical grading criteria for diabetic retinopathy.Multivariate logistic regression was used to analyze the correlative factors of DR and establish a DR risk prediction model.The validation group patient data were used into the model to assess the predictive power of the model.(2)TMT labeling combined with LC-MS/MS was used to analyze the protein profiling of vitreous humor from 6 proliferative diabetic retinopathy patients before and after intravitreal ranibizumab injection.GO annotation,Reactome pathway annotation,and protein-protein interaction analysis of differential proteins were performed using online databases(DAVID,metascape,and String).Enzyme-linked immunosorbent assay(ELISA)was used to detect the expressions of lumican,ITIH1 and CHI3L1.Results(1)Age(-4 to 0 points),duration of diabetes(0 to 13 points),systolic blood pressure(0 to 7 points),urea(0 to 3 points),chlorine(0 ~5 points),magnesium(-3 to 0 points),OGTT 2h C peptide(-6 to 0 points)and 24 h urine protein quantitation(0 to 11 points)were included in the DR risk prediction model,the total score ranged from-13 to 39 points.The diagnostic cut-off point was 11.5 points,with a sensitivity of 66.9% and a specificity of 66.6%,and the area under the ROC curve was 0.722(0.701-0.744).The sensitivity of the validation group was 63.8%,the specificity was 64.8%,and the area under the ROC curve was 0.683(0.615-0.751).(2)36 differential proteins were identified between the vitreous samples of PDR patients before and after intravitreal ranibizumab injection.35 proteins were up-regulated and 1 protein was down-regulated.GO annotations show that the major molecular function of differential proteins was binding,mainly biological processes were protein activation cascade,negative regulation of endopeptidase activity,and blood coagulation.Reactome pathway analysis showed that differential proteins were mainly involved in complement system activation,coagulation cascade activation,immune regulation,and platelet degranulation.The ELISA results showed that the concentration of lumican and ITIH1 increased after intravitreal ranibizumab injection,and the concentration of CHI3L1 decreased.Conclusions(1)Age,duration of diabetes,systolic blood pressure,urea,chlorine,magnesium,OGTT 2h C peptide and 24 h urine protein levels are risk factors of DR.The DR risk prediction model based on the above risk factors has certain prediction efficacy.This model can provide a scientific reference for DR prevention and screening.(2)The protein profiling of vitreous from PDR patients with intravitreal ranibizumab injection was changed.The function of differential proteins was involved in complement system activation,coagulation cascade,activation immune regulation,platelet degranulation and so on.The concentration of Lumican and ITIH1 were increased after ranibizumab injection,and the concentration of CHI3L1 was decreased after ranibizumab injection,suggesting that ranibizumab may regulate inflammation,angiogenesis and neuroprotection pathway related to these three proteins.