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Objective:To observe the expression and significance of Jagged1 in fibrovascular membranes of proliferative diabetic retinopathy (PDR).Methods:Sixty preretinal fibrovascular membrane specimens collected from fifty-seven patients (60 eyes) with PDR during vitrectomy in The Affiliated Hospital of Qingdao University from July 2014 to July 2015 were set as the PDR group.The patients were divided into the injection group (30 cases, 32 eyes) and non-injection group (27 cases, 28 eyes) according to whether they received anti-vascular endothelial factor drug intravitreally before surgery.Ranibizumab injections were administered to the patients in the injection group intravitreally 2-7 days before surgery.Eighteen macular epiretinal membrane specimens obtained from 18 non-diabetic patients were served as the control group.Hematoxylin-eosin staining was applied to observe the structural festures of specimers. The immunohistochemical staining was used to detect the expression levels of Jagged1, Delta-like 4(Dll4) and Notch1 in the injection and non-injection groups, and the real-time fluorescent quantitative polymerase chain reaction was performed to detect the relative expression levels of Jagged1, Dll4 and Notch1 mRNA in the three groups.Pearson linear correlation analysis was used to evaluate the relationships between the expression of Jagged1 mRNA and both Dll4 mRNA or Notch1 mRNA in the PDR fibrovascular membranes.This study protocol adhered to the Declaration of Helsinki and was approved by an Ethics Committee of The Affiliated Hospital of Qingdao University (No.QYFYWZLL25645). Written informed consent was obtained from each patient.Results:The neovascularization was found in fibrovascular membranes of PDR with a light microscope, and the lumen of the new blood vessels in the injection group was narrow, but relatively dilated in the non-injection group.There was no neovascularization found in the macular epiretinal membranes.The immunohistochemical staining revealed that there was the positive expression of Jagged1, Dll4 and Notch1 proteins in all PDR membranes, mainly located in the vascular endothelium during neovascularization.The absorbance values of Jagged1, Dll4 and Notch1 proteins were 6.25±1.82, 6.87±1.89 and 5.12±2.14 respectively in the non-injection group, which were all higher than 1.46±0.37, 1.55±0.24 and 1.32±0.53 respectively in the injection group, showing statistically significant differences ( t=5.168, P=0.014; t=6.012, P=0.008; t=3.453, P=0.030). There were statistically significant differences in Jagged1, Dll4 and Notch1 mRNA relative expression levels among the three groups ( F=77.337, 62.305, 51.869; all at P<0.01). The relative expression levels of Jagged1, Dll4 and Notch1 mRNA in the fibrovascular membranes with PDR were significantly higher than those of control macular epiretinal membranes, and the relative expression levels of Jagged1, Dll4 and Notch1 mRNA of the injection group were significantly lower than those of the non-injection group (all at P<0.05). The expression level of Jagged1 mRNA was positively correlated with expression levels of both Dll4 and Notch1 mRNA ( r=0.925, 0.950; both at P<0.05). Conclusions:There is a high expression of Jagged1 in the vascular endothelium of fibrovascular membranes with PDR and the Jagged1 expression is positively correlated with the expression of Dll4 and Notch1.The effect of Jagged1 on the neovascularization in PDR may be related to Dll4 and Notch1.
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Objective:To compare the protective effect of corneal protectant hydroxypropyl methylcellulose (HPMC) and balanced salt solution (BSS) on corneal epithelium in vitreous body surgery for proliferative diabetic retinopathy (PDR).Methods:A randomized controlled clinical trial was conducted.Fifty eyes of 50 patients with PDR who underwent minimally invasive vitrectomy in Xuzhou First People's Hospital from September 2018 to January 2019 were enrolled and randomly divided into HPMC group and BSS group, with 25 eyes in each group.All eyes underwent three-channel minimally invasive vitrectomy under non-contact wide-angle lens, and 2% HPMC and BSS were applied to keep the ocular surface moist according to grouping during the operation.The combination of cataract surgery, operation time, application times of 2% HPMC or BSS and the grade of corneal epithelial edema before and after operation were recorded.The patients were followed up for 1 month.Corneal fluorescein sodium staining and tear film break-up time (BUT) test were performed before operation and at 1 day, 3 days, 10 days and 1 month after operation.Schirmer Ⅰ test (SⅠt) and ocular surface disease index (OSDI) questionnaire were carried out before operation and at 1 month after operation.The study protocol adhered to the Declaration of Helsinki and was approved by an Ethics Committee of Xuzhou First People's Hospital (No.xyyⅡ[2018]005). Written informed consent was obtained from each patient prior to any medical examination.Results:The average frequency of application of eye drops in the HPMC group was (5.00±1.56) times, which was significantly less than (50.56±17.00) times in the BSS group ( t=-13.071, P<0.01). The postoperative corneal edema score of the HPMC group was 1.0 (1.0, 1.0) point, which was lower than 2.0 (2.0, 2.0) points of BSS group, and the difference was statistically significant ( Z=-4.909, P<0.01). There were statistically significant differences in postoperative corneal fluorescein sodium scores among 1 day, 3 days, 10 days and 1 month in the two groups (HPMC group: χ2=36.040, P<0.01; BSS group: χ2=50.892, P<0.01). The 1-, 3- and 10-day postoperative corneal fluorescein sodium scores in the HPMC group were significantly lower than those in the BSS group (all at P<0.05). One-day, 3-day, 10-day and 1-month postoperative BUT values were (6.15±2.20), (6.95±2.46), (6.16±2.11) and (5.81±2.92) seconds in the HPMC group, respectively, and were (3.89±1.87), (5.32±2.59), (5.01±2.12) and (4.97±2.10) seconds in the BSS group, respectively.There were significant differences in BUT between the two groups at different time points ( Fgroup=5.240, P<0.05; Ftime=2.846, P<0.05). The preoperative and 1-month postoperative SⅠt values in the BSS group were (12.24±5.55)mm and (9.96±4.53)mm, respectively, showing a statistically significant difference ( t=3.863, P=0.001). The postoperative OSDI score in the BSS group was (51.00±12.04) points, which was significantly higherly than the preoperative value of (47.89±10.95) points, and the difference was statistically significant ( t=-2.111, P<0.05). Conclusions:Compared with BSS, 2% HPMC in minimally invasive vitreous surgery has better protective effect on corneal epithelium of PDR, reduces the frequency of eye drop use during the surgery and shortens the repair time of ocular surface tissue after surgery.
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Objective@#To investigate the expression of proline hydroxylase 2 (PHD2) in the proliferatine membrane of proliferative diabetic retinopathy (PDR) and its relationship with PDR.@*Methods@#A prospective controlled clinical study was designed.The study included 8 PDR patients undergoing vitrectomy, 8 PDR patients receiving intravitreal injection of lucentis before vitrectomy, and 8 idiopathic macular epiretinal membrane (IMEM) patients without diabetes undergoing vitrectomy for in Inner Mongolia Autonomous Region People's Hospital which served as PDR group, lucentis group and control group, respectively proliferative membrane was obtained during the vitrectomy surgery.Hematoxylin-eosin staining was used for histologic observation, immunofluorescence was used to examine the expression of PHD2, vascular endothelial growth factors (VEGF), glial fibrillary acidic protein (GFAP) and platelet endothelial cell adhesion molecule-1 (PECAM 1/CD31). The fluorescence intensities of PHD2, VEGF and GFAP in proliferative membrane were compared among different groups.This study followed the Helsinki declaration and was approved by Medical Ethics Committee of Inner Mongolia Autonomous Region People's Hospital (No.20160603). Written informed consent was obtained from all subjects before entering the study.@*Results@#The morphology of PDR proliferative membrane was diversity, which consist of neovascularization, fibroblast-like cells, macrophages, neutrophils and lymphocytes, etc.The IMEM morphology proliferative membrane was mainly comsist of glial cells, with a small amount of fiber cells and macrophages.The membrane of lucentis group was observed with vascular atrophy and few fibroblast-like cells, vascular endothelial cells.PHD2, VEGF, GFAP and CD31 were all strongly positive expressed and co-expressed in the proliferative membrane of PDR.Besides, the glial cells aggregated in the film of non-perfused region, and the expression of GFAP in this area was obviously stronger than that in the well-perfused region; PHD2, VEGF, GFAP and CD31 were all weakly expressed in the proliferative membrane of lucentis group.Only in cell area, the expression of PHD2, VEGF and GFAP were weak in proliferative membrane.The fluorescence intensity of PHD2, VEGF and GFAP in proliferative membrane of control group were significantly different among the groups (all at P<0.001), and the fluorescence intensities of PHD2, VEGF and GFAP were significantly increased in the hyperplasia membrane of PDR group compared with those in lucentis group and control group (all at P<0.001).@*Conclusions@#PHD2, VEGF, GFAP and CD31 are all strongly expressed in the proliferative membrane of PDR.Lucentis can obviously decrease PHD2 expression.There may be pathways between VEGF and PHD2.Weak expression of PHD2 in IMEM membrane indicates that PHD2 is involved in the formation of IMEM.
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Objective To investigate the expression of proline hydroxylase 2 ( PHD2 ) in the proliferatine membrane of proliferative diabetic retinopathy ( PDR) and its relationship with PDR. Methods A prospective controlled clinical study was designed. The study included 8 PDR patients undergoing vitrectomy,8 PDR patients receiving intravitreal injection of lucentis before vitrectomy,and 8 idiopathic macular epiretinal membrane ( IMEM) patients without diabetes undergoing vitrectomy for in Inner Mongolia Autonomous Region People ' s Hospital which served as PDR group,lucentis group and control group,respectively proliferative membrane was obtained during the vitrectomy surgery. Hematoxylin-eosin staining was used for histologic observation, immunofluorescence was used to examine the expression of PHD2,vascular endothelial growth factors (VEGF),glial fibrillary acidic protein (GFAP) and platelet endothelial cell adhesion molecule-1 (PECAM 1/CD31). The fluorescence intensities of PHD2,VEGF and GFAP in proliferative membrane were compared among different groups. This study followed the Helsinki declaration and was approved by Medical Ethics Committee of Inner Mongolia Autonomous Region People's Hospital (No. 20160603). Written informed consent was obtained from all subjects before entering the study. Results The morphology of PDR proliferative membrane was diversity, which consist of neovascularization, fibroblast-like cells, macrophages,neutrophils and lymphocytes,etc. The IMEM morphology proliferative membrane was mainly comsist of glial cells,with a small amount of fiber cells and macrophages. The membrane of lucentis group was observed with vascular atrophy and few fibroblast-like cells, vascular endothelial cells. PHD2, VEGF, GFAP and CD31 were all strongly positive expressed and co-expressed in the proliferative membrane of PDR. Besides,the glial cells aggregated in the film of non-perfused region,and the expression of GFAP in this area was obviously stronger than that in the well-perfused region;PHD2, VEGF, GFAP and CD31 were all weakly expressed in the proliferative membrane of lucentis group. Only in cell area,the expression of PHD2,VEGF and GFAP were weak in proliferative membrane. The fluorescence intensity of PHD2, VEGF and GFAP in proliferative membrane of control group were significantly different among the groups (all at P<0. 001),and the fluorescence intensities of PHD2,VEGF and GFAP were significantly increased in the hyperplasia membrane of PDR group compared with those in lucentis group and control group (all at P<0. 001). Conclusions PHD2,VEGF,GFAP and CD31 are all strongly expressed in the proliferative membrane of PDR. Lucentis can obviously decrease PHD2 expression. There may be pathways between VEGF and PHD2. Weak expression of PHD2 in IMEM membrane indicates that PHD2 is involved in the formation of IMEM.
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@#AIM: To further investigate the etiology and treatment strategies of diabetic macular edema(DME)by studying the correlation between responses to intravitreal injection of Ranibizumab(IVR)and diabetic retinopathy(DR)extent in DME patients. <p>METHODS: This study comprised 33 eyes of 27 non proliferative diabetic retinopathy(NPDR)patients with DME and 34 eyes of 32 PDR patients with DME, who had been followed for at least 6mo after IVR. We compared the responses to the anti-VEGF treatment between the two groups. <p>RESULTS: NPDR patients had strong statistical improvement in best corrected visual acuity(BCVA)and central macular thickness(CMT)after both 3-month treatment and 6-month treatment(<i>P</i><0.05), While PDR patients had not(<i>P</i>>0.05). There were also statistical differences(<i>P</i><0.05)in BCVA and CMT between NPDR group and PDR at a time when the patients had received both 3-month treatment and 6-month treatment. <p>CONCLUSION: Different extents of DR have influence on DME responses to anti-VEGF.
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Background Pars plana vitrectomy (PPV) is the main therapy for advanced stage of proliferative diabetic retinopathy (PDR).Intravitreal injection of anti-vascular endothelial growth factor(VEGF) drug before PPV for PDR has been proved to decrease the occurrence of postoperative complications.However,the effect of conbercept on PPV was rarely reported.Objective This study was to observe the efficacy of intravitreal injection of conbercept (IVC) on PPV for PDR.Methods A nonrandomized control clinical trial was performed.A total of 47 PDR patients (51 eyes) undergoing PPV were enrolled in Yuebei People's Hospital from June 2015 to May 2016.All subjects were divided into IVC group (24 patients,26 eyes) and control group (23 patients,25 eyes).The incidence of iatrogenic retinal hole,rate of using intraocular tamponade,incidence of postoperative complications,central retinal thickness (CRT) and the best corrected visual acuity (BCVA) were comparatively analyzed.Results The incidence of iatrogenic retinal hole in IVC group was 7.69％,lower than 32.00％ in the control group,the difference was statistically significant (P=0.038).The percentage of using intraocular tamponade in IVC group was 19.23％,lower than 52.00％ in the control group,the difference was statistically significant (x2 =5.993,P =0.014).Four months after surgery,the incidence of postoperative vitreous re-hemorrhage in IVC group was significantly lower than that in the control group,the difference was statistically significant (P =0.024).Three months after surgery,the CRT in IVC group was (278.04 ± 43.46) μm,which is thinner than (340.76 ± 84.91) μm in the control group,the difference was statistically significant (t =-3.340,P =0.002).Three months after surgery,the BCVA in IVC group was better than that in control group,with significant difference between the two groups (Z =-2.114,P=0.034).No adverse effect was observed after IVC.Conclusions IVC before PPV for PDR can reduce the incidence of iatrogenic retinal hole and the rate of using intraocular tamponade,decrease the incidence of postoperative complications and macular retinal thickness,and improve the visual acuity.