Exploratory Study Of OCT Quantitative Parameters And Peripheral Blood Inflammatory Indices As Biomarkers In Diabetic Macular Edema

Chapter1 A nomogram based on peripheral blood inflammatory indices and OCT biomarkers for predicting the early efficacy of anti-VEGF therapy in patients with diabetic macular edemaObjectives:To investigate the roles of peripheral blood inflammatory indices and optical coherence tomography(OCT)biomarkers in diabetic macular edema(DME)patients’ early response to anti-vascular endothelial growth factor(VEGF),and to construct a nomogram based on the inflammatory clinical features.Methods:A total of 140 eyes from 93 patients with DME were included in this retrospective study,and all affected eyes received intravitreal anti-VEGF agent for three months at least.The best-corrected visual acuity(BCVA)were collected and OCT biomarkers were analyzed by Image J at baseline and three months after the initial injection.Peripheral blood inflammatory indices were calculated as well,including neutrophil-to-lymphocyte ratio(NLR),monocyte-to-lymphocyte ratio(MLR),platelet-to-lymphocyte ratio(PLR)and systemic immune-inflammation index(SII).Univariate and multivariate logistic regression analysis were adopted to explore factors that affect the poor early visual-functional response of patients with DME after anti-VEGF therapy.A nomogram was plotting to predict treatment response to anti-VEGF therapy for patients with DME.Model discrimination was evaluated by receiver operating characteristic(ROC)curve and areas under the curve(AUC),model calibration was assessed by the calibration curve and Hosmer-Lemeshow goodness-of-fit test,and the clinical usefulness of the model was assessed by using the clinical decision curve analysis(DCA).Results:40%(56/140)DME eyes showed poor visual-functional response following anti-VEGF treatment,and the multivariate logistic regression analysis revealed that older age(odds ratio(OR):1.09;95%confidence interval(CI):1.09-1.16;P=0.002),low baseline BCVA(logMAR)(OR:0.04;95%CI:0.01-0.17;P<0.001),triglycerides(TG)>2.055(OR:3.45;95%CI:1.21-9.85;P=0.021),NLR>2.57(OR:4.93;95%CI:1.24-19.65;P=0.024),PLR>98.93(OR:11.13;95%CI:1.75-70.72;P=0.011),the presence of subretinal fluid(SRF)(OR:0.2;95%CI:0.05-0.74;P=0.016),high external limiting membrane(ELM)disruption length(OR:1.01;95%CI:1.00-1.01;P=0.001),and a large number of hyperreflective foci(HRF)in the retinal outer layers(OR:1.13;95%CI:1.02-1.25;P=0.023)were independent risk factors for poor visual-functional response following anti-VEGF therapy(all P<0.05).The nomogram exhibited good predictive performance in DME patients after receiving anti-VEGF therapy with an AUC of 0.87(95%CI:0.812-0.928).The calibration curve indicated and the Hosmer-Lemeshow test showed a good fit to the model(P=0.77),and the DCA illustrated a good clinical utility.Conclusions:Circulating biomarkers and OCT imaging biomarkers can serve as inflammatory markers of DME,among which NLR>2.57,PLR>98.93,the presence of SRF,and a large number of HRF in the outer retinal layers were independent risk factors for poor visual-functional response following anti-VEGF therapy.Furthermore,the nomogram based on inflammatory clinical features can predict the early response to patients with DME,presenting excellent predictive efficiency and clinical utility.Chapter2 Study on diabetic macular edema in different OCT stages and its correlation with inflammatory indices and imaging biomarkersObjectives:To investigate the systemic inflammatory indices and imaging biomarkers of diabetic macular edema(DME)in different stages based on OCT parameters.Additionally,to analyse the effect on the early functional and anatomical outcomes after anti-VEGF treatment in different OCT stages.Methods:A total of 164 eyes from 111 patients with DME treated with anti-VEGF therapy for 3 consecutive months were enrolled in this retrospective study.We analyzed tomographic qualitative and quantitative features scored according to a protocol termed "TCED",including the central retinal thickness(CRT,"T"),the intraretinal cyst(IRC,"C"),the ellipsoid zone and external limiting membrane(EZ and ELM,"E")status,and the disorganization of the retinal inner layers(DRIL,"D").Based on the "TCED" grading system,DME was divided into four groups that is early,advanced,severe and atrophic stages.The best-corrected visual acuity(BCVA),subretinal fluid(SRF)and the number of hyperreflective foci(HRF)in the whole retinal layers were analyzed at baseline and three months after the first injection.Systemic inflammatory indices of peripheral blood were calculated,including neutrophil-to-lymphocyte ratio(NLR),monocyte-to-lymphocyte ratio(MLR),platelet-to-lymphocyte ratio(PLR),systemic immune-inflammation index(SII)and C-reactive protein(CRP).Statistical analysis were performed to compare systemic inflammatory indices,the decline in the proportion of imaging biomarkers(SRF and HRF)and the early efficacy of anti-VEGF therapy in different OCT stages relatively.Results:There were significant differences in systemic inflammatory indices among the four groups,including NLR,PLR,MLR,SII and CRP(all P<0.05).CRP in the atrophic stage was significantly higher than that in the advanced and severe stages(P=0.027,P=0.038);NLR and MLR in the atrophic stage were higher than that in the advanced stage(P=0.021,P=0.036),and SII in the early stage was higher than that in the advanced stage(P=0.045).Except for the atrophic stage,BCVA and CRT were significantly improved after treatment in early,advanced and severe stages(all P<0.05),especially in the severe stage.The decline in the proportion of SRF and HRF≥20 were the most significant in the advanced stage after anti-VEGF treatment(P<0.001,P=0.001),but not in the early,severe and atrophic stages(all P>0.05).Conclusions:There were differences in systemic inflammatory indices and the decline in the proportion of SRF and HRF in different stages based on OCT parameters,which can indirectly reflect the systemic and local inflammatory state.Meanwhile,the OCT-based staging can predict functional and anatomical prognosis of DME after anti-VEGF treatment,especially in the severe stage.The "TCED"grading system may be a biomarker for identifying risk stratification and management of DME.