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 effectiveness of probucol for non-proliferative diabetic retinopathy (NPDR) with hyperlipidemia. Methods Fifty-two patients (104 eyes) of NPDR with hyperlipidemia were enrolled in this study. The patients were randomly divided into treatment group and control group, 26 patients (52 eyes) in each group. Both groups received diet and exercise guidance, oral hypoglycemic agents and (or) intensive insulin therapy. After blood sugar and blood pressure were controlled, the treatment group received probucol 0.5 g, two times per day; and the control group received atorvastatin of 10 mg, one time per day. The total course was 12 months. Before and after one, three, six and 12 months, all patients underwent vision, ophthalmoscope, fundus fluorescein angiography, blood and urine tested. Variations of visual acuity, fundus condition, macular edema, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC) and 8-0HdG were observed before and after treatment. Results The total effective rate of visual prognosis were 44.23% and 40.38% in the treatment group and the control group, the difference had no statistical significacy (Z=-0.335, P＞0.05). Retinal hemorrhages and microaneurysms alleviated after treatment in both groups.The total efficiency of fundus prognosis was 65.38% in the treatment group and 36.54% in the control group, and the difference was statistically significant (Z=-2.973,P＜0.05). Macular edema was in six and five eyes in the treatment group and the control group respectively, which were lower than before treatment, the difference was statistically significant (chi;2=4.833, 4.300;P＜0.05). Between the two groups, the difference was not statistically significant (chi;2=0.102,P＞0.05). Twelve months after treatment, TG, TC and LDLC were decreased in the treatment group (t=15.653, 7.634, 14.871) and control group (t=13.275, 7.415, 13.632), and the difference was statistically significant (P＜0.05). HDLC showed no significant difference than before in the two groups (t=0.584, 0.275;P＞0.05). TG, TC, LDLC and HDLC showed no difference between the two groups (t=1.857, 0.133, 1.671, 0.875;P＞0.05). 8-0HdG decreased gradually during the one, three, six and 12 months in the treatment group (t=7.352,15.581, 27.324, 28.143) and control group (t=6.877, 8.672, 14.671, 14.855) after treatment, and the difference was statistically significant (P＜0.05). In the first month after treatment, 8-0HdG showed no difference between the two groups (t=0.513,P＞0.05). In the 3, 6, and 12 months after treatment, the 8-0HdG was lower in the treatment group than that in the control group, and the difference was statistically significant (t=3.434, 5.917, 5.226;P＜0.05). Conclusion In the treatment of NPDR with hyperlipidemia, probucol can reduce blood lipid, stable visual function and relieve macular edema.
Chronic central serous chorioretinopathy (CSC) usually demonstrates frequent recurrence, diffuse leakage and persistent subretinal fluid, which cannot be absorbed, thus lead to photoreceptor damage and poor visual acuity. As glucocorticoids have been implicated in the pathogenesis of chronic CSC, various anti-glucocorticoids oral drugs were used in the clinic to promote retinal fluid absorption and reduce the central retinal thickness of the macula and improve the vision outcomes. In addition, the 5α-reductase-specific inhibitor finasteride, the P450-3A4 inducer rifampicin, circadian rhythmic regulator melatonin, and systemic anti-inflammatory drug methotrexate have also been put into clinical trials for chronic CSC, and achieved certain effects. However, most of the clinical studies on these oral drugs were case reports, but not multi-center randomized clinical trials. The long-term effects of these oral drugs need to be observed and studied further.
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.
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 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 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)
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.
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.
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.
