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 evaluate the clinical efficacy of oral calcium dobesilate(CaD) on diabetic optic neuropathy (DON).Methods The clinical data of 235 eyes of 235 patients with DON diagnosed by examination of ocular fundus were retrospectively analyzed.The patients were divided into 3 groups according to the subtypes of DON: anterior ischemic optic neuropathy(AION)group(71 eyes of 71 patients), papilloedema group (71 eyes of 71 patients),and neovascularization of disc (NVD) group (93 eyes of 93 patients).The patients in each groups were randomly subdivided into CaD treating group and control group, in which the patients underwent oral administraion of CaD at a dose of 500 mg twice per day or Vit.E at a dose of 10 mg twice per day,respectively.The course of therapy was 6 months and consecutive 2 courses were performed with the 3-4 days interval between the courses; the courses lasted for 6 months.Several parameters (VFD/V),EA/d,NA/d,LA/d) were semiquantitative analyzed 2,4,6,8 months after initial treatment. Repeated ANOVA measures and t test were used as statistical methods.Results In CaD group,VFD/V (0.25plusmn;0.10),EA/d (0.94plusmn;0.53), and LA/d(1.83plusmn;1.12) 2 months after initial treatment was obviously better than the results before the treatment (0.49plusmn;0.13,1.57plusmn;0.71,3.42plusmn;1.88)(P＜0.001), respectively.VFD/V,EA/d and LA/d in CaD group 2,4,6,and 8 months after initial treatment significantly differed from which in the control group (P＜0.01). There was significant difference of VED/V,EA/d,and LA/d between the CaD and control group during the follow-up period (P＜0.01).At each time point in the followup period, there was no significant difference of NA/d among groups and between the treating and control group (P＞0.05).Conclusion Oral administration of CaD can rapidly and remarkably decrease the extent of visual field defect,relieve optic disc edema and lessen the leakage of NVD.
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 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.
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.
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.
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.
ObjectiveTo observe the effect of microincision vitrectomy assisted with intravitreaI injection of ranibizumab (IVR) in proliferative diabetic retinopathy (PDR) treatment. MethodsThis is a prospective, randomized, and comparative case series study. A total of 92 patients (92 eyes) with PDR were recruited to have microincision vitrectomy with (combined group) or without (PPV group) IVR. There are 48 eyes in the combined group and 44 eyes in the PPV group. The average operation time, iatrogenic breaks, the use of tamponade and electric coagulation, postoperative bleeding and best corrected visual acuity were comparatively analyzed among the two groups.The mean follow-up was (14.3±5.2) months. ResultsThe average operation time was (59.4±18.5) min in the combined group and (74.6±16.2) min in the PPV group. The rate of silicone oil tamponade (χ2=4.619), inert gas tamponade (χ2=4.290), electric coagulation (χ2=8.039) and iatrogenic breaks (χ2=4.330) in the combined group were significantly decreased compared with PPV group(P<0.05). The mean logMAR BCVA was 0.83±0.44 in the combined group and 1.37±0.53 in the PPV group, which significantly improved from preoperatively (t=3.257, 3.012; P<0.05). The rate of BCVA improvement in the combined group was significantly higher than that in the PPV group (t=2.972, P<0.05). The incidence of the recurrent vitreous hemorrhage was 2.1% in the combined group and 9.1% in the PPV group (χ2=6.741, P<0.05). There was no severe complication associated with surgery, such as choroidal detachment, retinal detachment and endophthal-mitis. ConclusionIVR before the microincision vitrectomy can shorten the operation time, reduce the use of electric coagulation and intraocular tamponade, and improve visual acuity for PDR patients.
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.
Chronic inflammation, oxidative stress and retinal ganglion cell apoptosis play important roles in the development of diabetic retinopathy. Fenofibrate, a peroxisome proliferator-activated receptor α agonist, is used for dyslipidemia. In addition to its lipid-modulating effects, fenofibrate also has anti-inflammatory, antioxidant, anti-apoptotic and anti-angiogenesis properties that may be useful to delay the progression of diabetic retinopathy. Some clinical studies have already confirmed that fenofibrate has therapeutic effect on diabetic retinopathy. Further studies the application of fenofibrate in the treatment of diabetic microangiopathy to clarify the safety and efficacy of fenofibrate is of great significance.