Objective To observe the effects of bevacizumab on aquaporin 4 (AQP4) expression in human retinal Muuml;ller cells in vitro under hypoxia. To explored the mechanism of treating retinal edema with bevacizumab. Methods Human Muuml;ller cells were cultured using the enzymatic digestion method. Transmission electron microscopic analysis and immunofluorescence staining identified Muuml;ller cells. With semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), the expression of AQP4 mRNA and vascular endothelial growth factor （VEGF） mRNA in Muuml;ller cells cultured under different concentration of COCl2 for different hours were observed. The expression of AQP4 mRNA in Muuml;ller cells cultured using CoCl2 precultured with 200 mu;g/ml bevacizumab was measured. Results More than 95% of primary cells showed positive reaction to glial fibrillary acidic protein, glutamine synthetase, vimentin and alpha;-smooth muscle actin with immunofluorescence staining. Characteristic 8-10 nm intracellular filaments could be seen in the cytoplasm viewed with transmission electron microscopy. The results using RT-PCR showed that CoCl2 increased the AQP4 and VEGF mRNA expression in Muuml;ller cells in a dose and time dependent manner (r=0.952, 0.954;P＜0.05). The expression of AQP4 mRNA in Muuml;ller cells was increased by VEGF (F=12.43,P＜0.05). The expression of AQP4 mRNA was significantly decreased by bevacizumab (F=2 370.37，P＜0.05). Conclusion Bevacizumab can down-regulate the expression of AQP4 mRNA in human Muuml;ller cells under hypoxic conditions partially by VEGF path, which may be a mechanism for treating retinal edema with bevacizumab.
ObjectiveTo evaluate the efficacy in the treatment of age-related macular degeneration (AMD) by bevacizumab versus ranibizumab.
MethodsA computerized search was conducted in the Embase, Ovid, PubMed, China National Knowledge Infrastructure (CNKI), WanFang Data and VIP database of Chinese journal. Randomized controlled trials (RCTs) comparing bevacizumab with ranibizumab for AMD from inception to November, 2013 were collected. Methodology qualifies of studies were performed by experienced reviewers according to the inclusion and exclusion criteria. Further, the materials were analyzed with software RevMan 5.2.6. Visual acuity and central foveal thickness before and 3, 6, 12 months after treatment between the two treatment methods were compared.
ResultsA total of 5 RCTs were included in this meta analysis, including 1954 patients (967 patients in the bevacizumab group, 987 eyes in the ranibizumab group). There was no difference in improving visual acuity after treatment between two groups [3 months: weighted mean difference (WMD)=0.32, 95% CI: -0.84 -1.49, P=0.59; 6 months: WMD=0.47, 95% CI: -0.67 -1.62, P=0.42; 12 months: WMD=0.84, 95% CI: -0.23 -1.90, P=0.12]. There was no difference in cutting down the central foveal thickness after treatment between two groups (3 months: WMD=6.21, 95% CI: -6.23-18.65, P=0.33; 6 months: WMD=4.06, 95% CI: -6.16-14.27, P=0.44; 12 months: WMD=-5.39, 95% CI: -14.41-3.63, P=0.24).
ConclusionBevacizumab has equal efficacy to ranibizumab in the treatment of AMD.
ObjectiveTo observe the efficacy of intravitreal injection of ranibizumab (IVR) for retinal angiomatous proliferation (RAP).
MethodsEleven patients (14 eyes) with RAP were enrolled in this retrospective clinical study. The best-corrected visual acuity (BCVA), central retinal thickness (CRT), and maximum retinal thickness (MRT) were detected by examination of visual acuity and optical coherence tomography (OCT). The average BCVA was 0.17±0.21, CRT was (382.71±219.07) μm, MRT was (746.36±268.29) μm. All eyes received 0.5 mg (0.05 ml) ranibizumab injection. Follow-up visits were performed monthly after injection. The mean follow-up time was (15.38±13.64) month. Injections were repeated if the eyes with retinal edema. The mean number of repetitive IVR was (3.7±1.0) times/eye (from 1 to 10 times). Changes in BCVA, CRT, MRT and complications were observed at the last follow up.
ResultsAt the last follow-up, the mean BCVA was 0.28±0.26 (from 0.01 to 1.0). Of 14 eyes, visual acuity improved in 11 eyes, not changed in 2 eyes and decreased in 1 eye. The difference of BCVA was significant between before and after the treatment (t=3.167,P=0.007). The mean CRT was (166.14±52.79) μm, which was less than that of pre-treatment values (t=3.737,P=0.002). The mean MRT was (360.43±102.19) μm, which was less than that of pre-treatment values (t=6.106,P=0.000). No ocular or systemic adverse effects occurred.
ConclusionIVR is an efficient and safe treatment for RAP, with visual acuity improvement, decrease of CRT and MRT.
Objective To observe the retinal toxicity of intravitreal injection of Bevacizumab (Avastin) in albino rabbit eyes at different doses. Methods Sixteen New Zealand albino rabbits，thirty-two eyes were divided into four groups at random. Three groups were prepared for Avastin experiment, named A, B, C. Each group received intravitreal injection of Avastin at dose 1.25 mg/0.05ml，2.5 mg/0.1ml and 6.25 mg/0.25 ml respectively. The other group named D served as a control, and accepted intravitreal injection of 0.9% normal saline 0.1 ml. Then test it by electroretinagram (ERG) after 1, 2 and 4 weeks. In addition, each group was removing two rabbitprime;s eyes to observe the retinal morphology and ultra structure by light microscope and transmission electron microscopy after intravitreal injection avastin 1, 2 and 4 weeks. Results The ERG pattern and amplitude of each group were normal after intravitreal injection Avastin 1, 2 and 4 weeks. （P＞0.05）Between study and control groups, there was no significant difference in retinal morphology which was observed by light microscope at any stage of the study. By electron microscopic observation, retinal ultramicrostructure was no evident retinal toxicity being tested both at group A and B (1.25 mg/0.05 ml and 2.5 mg/0.1 ml). But at group C (6.25 mg/0.25 ml), significant mitochondrial swelling and hydropic changes were seen in the inner segments of photoreceptors. And there was no improvement of the pathological changes in four weeks. Conclusion It is safe that intravitreal injection of Avastin in rabbitprime;s eyes at dose 1.25 mg or 2.5 mg at single time. （Chin J Ocul Fundus Dis，2008，24：193-196）
ObjectiveTo evaluate the macular visual function of patients with myopic choroidal neovascularization (MCNV) before and after intravitreal injection of conbercept.MethodsA prospective, uncontrolled and non-randomized study. From April 2017 to April 2018, 21 eyes of 21 patients diagnosed as MCNV in Shanxi Eye Hospital and treated with intravitreal injection of conbercept were included in this study. There were 9 males (9 eyes, 42.86%) and 12 females (12 eyes, 57.14%), with the mean age of 35.1±13.2 years. The mean diopter was ?11.30±2.35 D and the mean axial length was 28.93±5.68 mm. All patients were treated with intravitreal injection of conbercept 0.05 ml (1+PRN). Regular follow-up was performed before and after treatment, and BCVA and MAIA micro-field examination were performed at each follow-up. BCVA, macular integrity index (MI), mean sensitivity (MS) and fixation status changes before and after treatment were comparatively analyzed. The fixation status was divided into three types: stable fixation, relatively unstable fixation, and unstable fixation. The paired-sample t-test was used to compare BCVA, MI and MS before and after treatment. The x2 test was used to compare the fixation status before and after treatment.ResultsDuring the observation period, the average number of injections was 3.5. The logMAR BCVA of the eyes before treatment and at 1, 3, and 6 months after treatment were 0.87±0.32, 0.68±0.23, 0.52±0.17, and 0.61±0.57, respectively; MI were 89.38±21.34, 88.87±17.91, 70.59±30.02, and 86.76±15.09, respectively; MS were 15.32±7.19, 21.35±8.89, 23.98±11.12, 22.32±9.04 dB, respectively. Compared with before treatment, BCVA (t=15.32, 18.65, 17.38; P＜0.01) and MS (t=4.08, 3.50, 4.26; P＜0.01) were significantly increased in the eyes 1, 3, and 6 months after treatment. There was no significant difference in the MI of the eyes before treatment and at 1, 3, and 6 months after treatment (t=0.60, 2.42, 2.58; P＞0.05). Before treatment and at 1, 3, and 6 months after treatment, the proportion of stable fixation were 28.57%, 38.10%, 38.10%, 33.33%;the proportion of relatively unstable fixation were 47.62%, 47.62%, 52.38%, 57.14% and the proportion of unstable fixation were 23.81%, 14.28%, 9.52%, 9.52%, respectively. The proportion of stable fixation and relatively unstable fixation at 1, 3 and 6 months after treatment were higher than that before treatment, but the difference was not statistically significant (x2=1.82, 1.24, 1.69; P＞0.05).ConclusionBCVA and MS are significantly increased in patients with MCNV after intravitreal injection of conbercept.
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 influencing factors on clinical response to conbercept for diabetic macular edema (DME).MethodsA total of 51 patients (51 eyes) with DME who underwent intravitreal injection of conbercept were included in this retrospective study. The general information (age, sex, body mass index, smoking history, drinking history), blood glucose indicators (duration of diabetes, fasting blood glucose, HbA1c), blood pressure indicators (history of hypertension, systolic blood pressure, diastolic blood pressure), lipid indicators [total cholesterol (TC), high-density lipoprotein (HDL), apolipoprotein A (APOA)], biochemical indicators [neutrophil concentration, hemoglobin (HB), serum creatinine (Scr)] were collected. The best corrected visual acuity (BCVA) and macular central macular thickness (CMT) before and after treatment were comparatively analyzed. CMT reduced not less than 20% and BCVA increased by 2 lines as effective standards. Univariate analysis and multivariate logistic regression analysis were used to determine the factors affecting the efficacy of intravitreal injection of conbercept in patients with DME.ResultsUnivariate analysis showed that diastolic blood pressure, HDL, serum neutrophil concentration, baseline CMT and baseline BCVA were associated with edema regression (P＜0.05); HbA1c was associated with vision improvement (P＜0.05). Multivariate logistic regression analysis showed that there was a history of smoking (OR=0.122, 95% CI 0.017 ? 0.887), low diastolic blood pressure (OR=0.850, 95%CI0.748 ? 0.966), low HDL (OR=0.007, 95%CI 0.000 1 ? 0.440), thin baseline CMT (OR=0.986, 95%CI0.977 ? 0.995) were independent risk factors for failure outcome of edema regression (P＜0.05); long duration of diabetes (OR=1.191, 95%CI 1.011 ? 1.404), high APOA (OR=1.007, 95% CI 1.000 ? 1.013) were independent risk factors for failure outcome of vision improvement. Age, fasting blood glucose, systolic blood pressure, TC, HB, Scr and other indicators had no effect on the efficacy of edema regression and vision improvement after treatment (P＞0.05).ConclusionsSmoking history, long duration of diabetes, low diastolic blood pressure, low HDL level, high APOA level and thin baseline CMT are independent risk factors for the treatment of DME with intravitreal injection of conbercept.
ObjectiveTo observe the efficacy of adjuvant intravitreal injection of anti-vascular endothelial growth factor (VEGF) therapy for advanced Coats disease.
MethodsThis study is a retrospective case series study. Fourteen patients (14 eyes), presenting Coats Stages 3B and 4 (8 and 6 eyes, respectively) were enrolled. All the patients were treated with adjuvant intravitreal anti-VEGF therapy. The intravitreal anti-VEGF injections varied from 1 to 7, with a median injections of 2.14. In 14 eyes, combined therapy was subretinal fluid drainage in 4 eyes, photocoagulation in 2 eyes, vitrectomy in 8 eyes. The follow-up period was ranged from 4 to 36 months, with a median follow-up of 18.8 months. Visual acuity and retinal reattachment were observed in follow up.
ResultsAt last follow up, global suvival was 100.0% with no enucleation performed in any patient because of disease progression. Except for 2 children who were unable to cope with the visual acuity test, visual acuity was improved in 2 patients, stable in 8 patients, and decreased in 2 patients. 5 patients (35.7%) achieved in complete retinal reattachment, 3 patients (21.4%) were succeed in partial retinal reattachment, and the remain 6 patients(42.8%) failed in retinal reattachment. Two patients developed cataract after vitrectomy, and no other adverse reaction was observed during follow-up.
ConclusionAnti-VEGF therapy combined with classic treatments in advanced Coats disease can keep or impove the visual acuity in most patients by reducing of subretinal exudation.
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 concentration of the inflammatory cytokines in vitreous of severe proliferative diabetic retinopathy (PDR) after intravitreal ranibizumab injection (IVR).
MethodsA total of 80 PDR patients (80 eyes) were enrolled in this study. The patients were randomly divided into vitrectomy group (group A) and IVR combined with vitrectomy group (group B), 40 eyes in each group. The differences of sex (χ2=0.05), age (t=0.59), duration of diabetes (t=0.36), HbA1c (t=0.13) and intraocular pressure (F=0.81) between two groups were not significant (P>0.05). The eyes in group B received 0.5 mg (0.05 ml) ranibizumab injection at 7 days before operation. The vitreous samples (0.4 ml) were obtained before operation. The concentration of vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-8, intercellular adhesion molecule-1 (ICAM-1) and connective tissue growth factor (CTGF) were measured by enzyme-linked immunosorbent assays.
ResultsThe concentration of VEGF and ICAM-1 were (10.70±3.60), (224.64±90.32) pg/L in group B and (72.38±23.59), (665.61±203.34) pg/L in group A. The differences of VEGF and ICAM-1 concentration between two groups was significant (t=16.34, 12.53; P<0.001). The concentration of IL-6 and IL-8 were (210.64±80.27), (156.00±57.74) pg/L in group B and (45.78±33.82), (41.07±13.82) pg/L in group A. The differences of IL-6 and IL-8 concentration between two groups was significant (t=11.97, 12.24; P<0.001). There was no difference of CTGF concentration between two groups (t=1.39, P=0.17). The CTGF/VEGF in group B was higher than that in group A (t=14.75, P<0.001).
ConclusionsOne week after IVR, the concentration of VEGF and ICAM-1 are decreased, while IL-6 and IL-8 increased. There is no obvious change in CTGF, but CTGF/VEGF is increased.
