ObjectiveTo observe the effect of preoperative intravitreal ranibizumab injection (IVR) on the operation duration of vitrectomy and postoperative vision for the treatment of proliferative diabetic retinopathy (PDR). MethodsA prospective study was carried out with the 90 PDR patients (90 eyes) who underwent vitrectomy. The 90 patients(90 eyes)were assigned to the vitrectomy only group(43 eyes) and the IVR combined with vitrectomy group (47 eyes). The IVR was performed 5-13 days prior to vitrectomy in the IVR combined with vitrectomy group. There were 15 eyes with fibrous proliferation PDR (FPDR), 16 eyes with advanced PDR (APDR) without involving the macular and 16 eyes with APDR involving the macular in the vitrectomy only group. There were 14 eyes with FPDR, 15 eyes with APDR without involving the macular and 14 eyes with APDR involving the macular patients in the IVR combined with vitrectomy group. All the eyes in the two groups were regularly operated by the same doctor to complete the vitrectomy. The start and end time of vitrectomy were recorded. The average follow-up time was 10 months. The changes of best corrected visual acuity (BCVA) before and 1, 3 and 6 months after surgery were compared between the two groups. ResultsThe duration of operation of the FPDR type (t=-8.300) and the APDR involving the macular type (t=-2.418) in the IVR combined with vitrectomy group was shorter than vitrectomy only group (P < 0.05). The comparison of duration of operation of the APDR without involving the macular type in the two groups has no statistically significant difference (t=-1.685, P > 0.05). At 1 month after surgery, the comparison of BCVA of the IVR combined vitrectomy group and the vitrectomy only group in APDR involving the macular type has no statistically significant difference (t=0.126, P > 0.05). At 3, 6 months after surgery, the BCVA of the IVR combined vitrectomy group in APDR involving the macular type was significantly better than the BCVA of the vitrectomy only group (t=8.014, 7.808; P < 0.05). At 1, 3, and 6 months after surgery, the BCVA of the IVR combined vitrectomy group in FPDR type (t=3.809, 1.831, 0.600) and APDR without involving the macular type (t=0.003, 1.092, 3.931) compared with pre-treatment, the difference were not statistically significant (P > 0.05); the BCVA in APDR without involving the macular type compared with pre-treatment, the difference was distinctly statistically significant (t=2.940, 4.162, 6.446; P < 0.05); the BCVA in APDR involving the macular type (t=0.953, 1.682, 1.835) compared with pre-treatment, the difference were not statistically significant (P > 0.05). ConclusionPreoperative IVR of PDR can shorten the operation duration and improve the BCVA of APDR involving the macular type.
Objective To observe the efficiency and safety of a single intravi treal injection of Bevacizumab (Avastin) in patients with diabetic macular edema. Methods Prospective, open label study of 18 eyes of 18 patients with diabetic macular edema which was diagnosed by examination of regular inspection, fundus fluorescein angiography(FFA) and optic coherence tomography(OCT). The patients without general or partial surgery contraindications, aged from 34-75 years with a mean age of 54plusmn;11 years. The best corrected visual acuity of logMAR was 1.023plusmn;0.45 and the retinal thickness of macular foveal was 486 mu;m before the treatment. The eyes have intravitreal injection with Bevacizumab at dose 1.5 mg (0. 06 ml). After the treatment, the follow-up period ranging from 12 to 20 weeks (m e an 16plusmn;4 weeks). The changes of visual acuity, intraocular pressure, OCT and FFA before and after the treatment were observed and analyzed. Results All 18 patients had a mean logMAR BCVA of 1.023plusmn;0.45 at baseline and at the follow-up weeks 1, 4, 12, the mean logMAR BCVA was significantly improved as 0.864plusmn;0.48 （P=0.001）, 0.739plusmn;0.51 (P=0.003), 0.792plusmn;0.50 (P=0.015) respectively, and the differences are statistically significant compared with before. Sixteen eyes (88.9%) had a improved or stable visual acuity, the BCVA increased 2 lines (0.2 logMAR vision) or better in 10 eyes (55.6%) and decreased in 2 eyes at 12 weeks after injection. OCT demonstrated that retinal thickness of macular foveal decreased from 486 mu;m to 413 mu;m at 4 weeks, decreased to 383mu;m at 12 weeks（P=0.002， P=0.001）, and the differences are statistically significant compared with before. There are remarkable resolution of central retinal edema in 13 eyes (72.2%) at 12 weeks after the injection. No local or systemic adverse events were observed in any patients. Conclusions The preliminary result in our observati on showed that int ravitreal injection of Bevacizumab therapy was well tolerated with a significant improvement in BCVA and decrease in macular edema for patients with diabetic macular edema. A randomly controlled multicenter clinical trial is necessary. (Chin J Ocul Fundus Dis,2008,24:172-175)
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 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.
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）
Objective To observe the preventing effect of intraocular injection of Bevacizumab (Avastin) to retinal microvascular proliferation in non-obese diabetes mice. Methods In the study, thirty non-obese diabetes mice (NOD mice) were selected. The left eyes of mice were selected as treatment group with 1mu;l A vastin (25mg/1ml) injected, and right eyes were selected as control group with 1 mu;l saline injected. One week, one month, two months after injection, ten mice were selected randomly, and then enucleated two eyes, in which the retinal microvascular endothelial cells ultrastructure and immunohistochemistry of retinal CD34 and VEGF, were observed and measured. The differences of dense of positive sta ining between two groups were compared by digital image analysis. Results The positive expression of VEGF and CD34 were brown staining, and the positive staining of CD34 located in vascular endothelial cells. There was statistically significant difference in VEGF expression between two groups in 1 week and 1 month after injection（t=21.6, t=13.5; P＜0.01), and no statistically significant difference in 2 months after injection （t=0.9, P＞0.05）. There was statistically significant difference in CD34 expression between two groups in 1 month and 2 months af ter injection（t=3.2, P＜0.01; t=2.7, P＜0.05） and no statistically significant difference in 1 week after injection（t=1.3, P＞0.05）. In every time point after injection, there was no obvious change in the microstructure of retinal vascular endothelial cells. Conclusion Intraocular injection of Avastin could prevent the abnormal proliferation of retinal microvascular in NOD mice. （Chin J Ocul Fundus Dis，2008，24：180-183）
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.