Laser photocoagulation, intravitreal injection of antibody against vascular endothelial growth factor (VEGF) or corticosteroids and pars plana vitrectomy are current popular therapeutic approaches for diabetic retinopathy (DR). However, some DR patients still progress to irreversible blindness even after the above treatments which do not aim at the pathological mechanisms and influence factors for DR. Thus, with the further elucidation on the molecular pathological mechanisms and overall understanding of the factors affecting DR development, more and more potential therapeutic interventions such as neuron protection, vascular reconstruction and protection, gene therapy, non-VEGF dependent anti-neovascularization agents have been explored. Individual precise therapy based on the potential therapeutic targets would provide the promising future for DR patients.
ObjectiveTo observe the clinical effect of microincision vitreoretinal surgery (VRS) assisted with intravitreal injection of ranibizumab (IVR) in severe proliferative diabetic retinopathy (PDR) treatment. MethodsThis is a prospective non-randomized controlled clinical study. A total of 60 patients (70 eyes) with severe PDR diagnosed were enrolled and divided into IVR group (31 patients, 35 eyes) and control group (29 patients, 35 eyes). IVR group patients received an intravitreal injection of 0.05 ml ranibizumab solution (10 mg/ml) first, and 3 or 4 days later they received 23G microincision VRS. Control group patients only received 23G microincision VRS. The follow-up time was 3 to 12 months with an average of (4.5±1.8) months. The logarithm of the minimal angle of resolution (logMAR) best corrected visual acuity (BCVA), intraocular pressure, the central retinal thickness (CRT) and retinal reattachment, and the incidence of postoperative complications were comparatively analyzed. ResultsThere was no topical and systemic adverse reactions associated with the drug after injection in IVR group. The incidence of post-operative vitreous hemorrhage (VH) in IVR group and control group was 8.6% and 28.6% at 1 week after surgery, 0.0% and 17.1% at 1 month after surgery, 0.0% and 8.6% at 3 month after surgery respectively. The differences were statistically significant for 1 week (χ2=4.63, P < 0.05) and 1 month (χ2=4.56, P < 0.05), but was not statistically significant for 3 months (χ2=0.24, P > 0.05). The mean post-operative logMAR BCVA of IVR group (0.81±0.40) and control group (1.05±0.42) have all improved than their pre-operative BCVA, the difference was statistically significant (t=12.78, 4.39; P < 0.05). The mean logMAR BCVA of IVR group is higher than BCVA of control group, the difference was statistically significant (t=-2.36, P < 0.05). The average post-operative CRT in IVR group was thinner than that of control group, the difference was statistically significant (t=-2.53, P < 0.05). The incidence of a transient high intraocular pressure in IVR group (14.3%) was lower than that in control group (34.3%), the difference was statistically significant (t=4.79, P < 0.05). The incidence of retinal reattachment (t=0.35), epiretinal membrane (χ2=0.97), neovascular glaucoma (χ2=0.51) was no difference between these two groups (P > 0.05). ConclusionThe minimally invasive VRS assisted by IVR treatment for severe PDR can effectively prevent postoperative VH, reduce CRT and improve visual acuity.
Objective To observe the synergistic effect of metformin and anti-vascular endothelial growth factor (VEGF) in the treatment of diabetic retinopathy. Methods This study was composed of clinical data review and in vitro cell experiment. Ten patients (12 eyes) with diabetic macular edema treated with anti-VEGF drugs were included in the study. Patients were randomly divided into the VEGF group (anti-VEGF drug therapy) and the combined treatment group (anti-VEGF drug combined with metformin). The changes of visual acuity and central retinal thickness (CRT) were compared between the two groups. As far as the in vitro experiment was concerned, vascular endothelial cells were divided into the control group (normal cells), the VEGF group (50 ng/ml VEGF), the anti-VEGF group (50 ng/ml VEGF+2.5 μg/ml of conbercept), and the combined group (50 ng/ml VEGF +2.5 μg/ml of conbercept +2.0 mmol/L of metformin). And then MTT cell viability assay, scratch assay and real-time quantitative polymerase chain reaction assay were performed to analyze the cell viability, cell migration and mRNA level of VEGFR2, protein kinase C (PKC)-α and PKC-β successively. ResultsReview of clinical trial shows that the CRT recovery rates in the combined treatment group were much higher than that in the VEGF group at 3 month after the operation, while the difference was statistically significant (t=−2.462, P＜0.05). In vitro cell experiment results showed that VEGF induction upregulated the viability and mobility of vascular endothelial cells obviously compared with control group, at the same time, the use of anti VEGF drugs can effectively reverse the trend, in contrast, combination of metformin and anti-VEGF showed a more superior effect to some extent (P＜0.05). In the VEGF group, the mRNA expression of VEGFR2, PKC-αand PKC-β were significantly increased compared with the control group (P＜0.01); while the mRNA expression of VEGFR2, PKC-αand PKC-β in the combination group decreased significantly compared with the VEGF group and the control group (P＜0.05). However, in the anti-VEGF group, the mRNA expression of VEGFR2, PKC-αand PKC-β were decreased, but has failed to reach the level of statistical learn the difference. ConclusionsThe combination of metformin and anti-VEGF drugs can reduce the CRT of diabetic retinopathy patients and inhibit the proliferation and migration of retinal vascular endothelial cells which induced by VEGF. The synergistic mechanism may be related to the inhibitory effect of metformin on the expression of VEGFR and PKC.
ObjectiveTo analyze the concentrations of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in aqueous humor of patients with proliferative diabetic retinopathy (PDR) before and after intravitreal injection of ranibizumab. MethodsTwenty-five eyes of 20 PDR patients were collected as the PDR group. Twenty-five eyes of 21 senile cataract patients were collected as the control group. There were no statistical significance in gender (χ2=0.223), age (Z=-1.555) and intraocular pressure (Z=-0.225) between the two groups (P > 0.05). Samples of aqueous humor (0.1 ml) were collected just before and 7 days after the injection of ranibizumab in PDR group. Samples of aqueous (0.1 ml) humor were collected just before cataract surgery in control group. The concentrations of VEGF and PEDF in the aqueous humor were measured by enzyme-linked immunosorbent assay. ResultsThe VEGF and PEDF concentration in the aqueous humor were reduced significantly after intravitreal injection of ranibizumab in PDR group (Z=-4.072, -4.319; P < 0.05). The concentrations of VEGF and PEDF in the aqueous humor before intravitreal injection of ranibizumab in PDR group were significantly higher than the control group (Z=-5.228, 4.706; P < 0.05). The VEGF concentration in the aqueous humor after intravitreal injection of ranibizumab in PDR group were similar to control group (Z=-1.557, P > 0.05). However, the concentration of PEDF in the aqueous humor after intravitreal injection of ranibizumab in PDR group still higher than control group (Z=-2.475, P < 0.05). The ratio of VEGF/PEDF before and after intravitreal injection of ranibizumab was statistically different (Z=-2.058, P < 0.05), but was the same between PDR group and control group (Z=-0.456, -0.844; P > 0.05). The aqueous humor concentrations of VEGF and PEDF were not significantly correlated with each other, neither in PDR group (r=-0.195, -0.174; P > 0.05) nor in control group (r=-0.286, P > 0.05). ConclusionsAqueous humor concentrations of VEGF and PEDF are significantly elevated in eyes with PDR. Intravitreal injection of ranibizumab significantly decreased the VEGF and PEDF in the aqueous humor after 7 days.
Objective To observe the effect of resveratrol on retinal vasculopathy in diabetic rats. Methods Forty-five Sprague-Dawley male rats were randomly divided into the resveratrol group, treatment control group and the normal control group, 15 rats in each group. Diabetic rat models were induced with streptozotocin injection in resveratrol group and treatment control group. The same volume of sterile saline solution was injected into the rats of the normal control group. The rats of resveratrol group and treatment control group were feed with highfat diet. The rats of resveratrol group received oral gavage of resveratrol (75 mg/kg) twice a day for four months. The same volume of sterile saline solution was given by gavage in rats of treatment control group twice a day for four months. 2 ml femoral vein blood and 50 mu;l aqueous fluid of anterior chamber of the eye from rats of three groups were collected to detect fasting blood glucose, aqueous fluid glucose, cholesterol and triglyceride. The retinal vascular permeability was test by labeling with evans blue. Whole retina was isolated to detect the pericyte number. Total protein was extracted from retina to test the level of vascular endothelial growth factor (VEGF). Results The fasting blood glucose, aqueous fluid glucose, cholesterol and triglyceride in treatment control group were higher than those in normal control group, also higher than those in resveratrol group except cholesterol. The differences among the three groups were statistically significant (F=152.809, 65.230, 3.861, 15.059; P＜0.05). The retinal vascular permeability in treatment control group was higher than that in normal control group, while it in resveratrol group was lower than that in treatment control group. The differences among the three groups was statistically significant (F=11.626,P＜0.05). The pericyte number in treatment control group decreased as compared to normal control group, while it in resveratrol group increased as compared to treatment control group. The differences among the three groups was statistically significant (F=43.284, P＜0.05). The VEGF expression in treatment control group increased as compared to normal control group, while it in resveratrol group decreased as compared to treatment control group. The differences among the three groups was statistically significant (F=14.017, P＜0.05). Conclusion Resveratrol can improve abnormal retinal vasculopathy structure and function, down-regulated level of fasting blood glucose, aqueous fluid glucose, triglyceride and VEGF may be the mechanism.
ObjectiveTo observe the clinical effect of intravitreal ranibizumab (IVR) combined with vitrectomy in treating proliferative diabetic retinopathy (PDR). MethodsThis is a prospective non-randomized controlled clinical study. A total of 62 patients (70 eyes) who underwent vitrectomy for PDR were enrolled and divided into IVR group (30 patients, 34 eyes) and control group (32 patients, 36 eyes).IVR group patients received an intravitreal injection of 0.05 ml ranibizumab solution (10 mg/ml) 3 or 5 days before surgery. The follow-up time was 3 to 18 months with an average of (4.5±1.8) months. The surgical time, intraoperative bleeding, iatrogenic retinal breaks, use of silicone oil, the best corrected visual acuity (BCVA) and the incidence of postoperative complications were comparatively analyzed. ResultsThe difference of mean surgical time (t=6.136) and the number of endodiathermy during vitrectomy (t=6.128) between IVR group and control group was statistically significant (P=0.000, 0.036). The number of iatrogenic retinal break in IVR group is 8.8% and control group is 27.8%, the difference was statistically significant (χ2=4.154, P=0.032). Use of silicone oil of IVR group is 14.7% and control group is 38.9%, the difference was statistically significant (χ2=5.171, P=0.023). The incidence of postoperative vitreous hemorrhage in 3 month after surgery was 11.8% and 30.6% respectively in IVR group and control group. The differences were statistically significant (χ2=3.932, P=0.047). The 6 month postoperative mean BCVA of IVR group and control group have all improved than their preoperative BCVA, the difference was statistically significant (t=4.414, 8.234; P=0.000).But there was no difference between the mean postoperative BCVA of two groups (t=0.111, P=0.190). There was no topical and systemic adverse reactions associated with the drug after injection in IVR group. ConclusionsMicroincision vitreoretinal surgery assisted by IVR for PDR shorten surgical time, reduces the intraoperative bleeding and iatrogenic retinal breaks, reduces the use of silicon oil and the postoperative recurrent vitreous hemorrhage. But there was no significant relationship between vision improvement and IVR.
Objective To observe the effect of Fufang XueShuanTong (FXST) on prevention for retinal microangiopathy of diabetic rats. Methods Take the normal male Wistar rats as normal control group; take the streptozotocin (STZ) Wistar rats as diabetic model group. And then the diabetic model group was divided into two groups: diabetic control group (without other treatment) and FXST treatment group (with FXST at dose 900 mg/kg, by the way of given medicine from esophagus to stomach, 1 time/day, experimental period was 20 weeks). When all the animals had been raised for 20 weeks, not only retinal digesting preparations were used, the endothelium/pericyte ratio (E/P ratio) and micro-vascular changes were observed by microscope, vascular relative area were measured by image system，but also the thickness of capillary basement membrane, the ultrastructural changes of endothelium and pericyte were observed by transmission electron microscope. Results On the 20th week, retinal digesting preparations showed that acellular capillaries, irregular vessel nets, segmental expansion, segmental stricture even occlusion, pericyte number decreased obviously, E/P ratio increased, vascular relative area increased and ghosts of pericytes etc in diabetic control group. Compared to diabetic control group, the retinal changes of FXST treatment group was lighter, the E/P ratio and vascular relative area were closer to normal control group. Transmission electron microscopy results showed that thickness of basement membrane was increased in DM group, vascular changes was light in FXST treated group. Conclusions FXST can prevent the changes of micrangium in diabetic rats effectively. （Chin J Ocul Fundus Dis，2008，24：272-275）