Objective To compare the clinic therapeutic effect of intravitreal ranibizumab injection versus photodynamic therapy (PDT) combined with intravitreal ranibizumab injection for idiopathic choroidal neovascularizatio (ICNV), and to investigate the clinical effect and safety of treatment. Methods A randomized controlled clinical prospective study was performed for 27 patients (27 eyes) diagnosed as ICNV. Fourteen patients were assigned to receive PDT and intravitreal ranibizumab injection (combination roup.n=14); the control group was treated with only intravitreal ranibizumab injection (single group, n=13).The combination group was treated with an intravitreal injection of ranibizumab (0.5 mg/0.05 ml) 1 week after PDT. The bestcorrected visual acuity (BCVA) (logMAR), examination of the ocular fundus, fluorescence fundus angiography (FFA), indocyanine green angiography (ICGA) and optical coherence tomography (OCT) were performed respectively at 1, 2, 3, 6 and 12 months after treatment. If choroidal neovascularization (CNV) was only partially regressed or the leakage went on during follow-up, those patients were re-injected with ranibizumab. Results After 12 months, the average vision is 0.22plusmn;0.11 in single group, and 0.21plusmn;0.12 in combination group, and the differences were not significant (t=0.187, P=0.853). In single group FFA and ICGA showed completely closed CNV in 10 eyes (77.92%), and almost closed CNV in 3 eyes (23.08%) with obvious reduction of fluorescence leakage. In combination group FFA and ICGA showed completely closed CNV in 12 eyes (85.71%), and almost closed CNV in 2 eyes (14.29%) with obvious reduction of fluorescence leakage; OCT showed the subretinal fluid absorption and reduction of CNV. The average macular retinal thickness (MRT) in single groups is （167.96plusmn;10.69） m, and in combination groups is （171.64plusmn;11.30）m. In single and combination groups MRT decreased significantly at the final follow-up, but no significant differences in both groups (t=-0.887.P=0.389). The average number of intravitreal injection was （1.5plusmn;0.7） in combination group and （2.4plusmn;1.0） in single group (t=2.821，P=0.009). There were no ocular or systemic adverse events observed except for one patient with subconjunctival hemorrhage in the single group.Conclusions Intravitreal ranibizumab injection and PDT combined with intravitreal bevacizumab injection are both effective and safe for the patients with ICNV. The combined therapy can induce CNV regression, fundus hemorrhage and exudation absorption more effectively, and have less recurred CNV and side effects.
Objective To observe the effects of dual targets intervention on the expression of vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) in diabetic rat retina. Methods Forty-eight Sprague -Dawley rats were randomly divided into control group (CON1 group) and diabetes mellitus group (DM group). The rats of DM group were induced with streptozotocin injection creating a diabetic model. Retinas were obtained at eight, 10, 12 weeks after DM induction from both groups. CTGF and VEGF mRNA levels were examined by realtime reverse transcriptionpolymerase chain reaction (RT-PCR). Based on the results of above experiments, 60 rats with same conditions were selected. Fifty rats were induced with streptozotocin injection creating a diabetic model, and 10 rats comprised the control group (CON2 group). Then the 50 diabetic rats were randomly divided into ranibizumab and CTGF shRNA dual targets intervention group, ranibizumab singletarget intervention group, CTGF shRNA singletarget intervention group and nonintervention group. Retinas were obtained at one week after intervention from all the groups. CTGF and VEGF mRNA levels were examined by RT-PCR. Results The levels of CTGF mRNA were significantly higher in DM group than that in CON1 group at the 8th weeks after DM induction, and this upregulation was maintained through the 12th week (t=-2.49, -2.67, -2.42;P＜0.05). There was no difference on VEGF mRNA levels between DM group and CON1 group at the 8th weeks after DM induction(t=-0.443,P=0.669). VEGF mRNA levels of DM group started to be significantly elevated over those in the CON1 group at the 10th week, and remained to be higher at the 12th week (t=-2.35, -2.57;P＜0.05). The VEGF mRNA of ranibizumab single-target intervention group was significantly lower than that in non-intervention group (t=-3.44,P=0.014), which was similar to CON2 group (t=-1.37,P＞0.05); however, the CTGF mRNA level was significantly increased as compared to the nonintervention group (t=2.48,P＜0.05). In the CTGF shRNA single-target intervention group, the levels of CTGF and VEGF mRNA were decreased as compared to the non-intervention group (t=0.23, -2.92;P＜0.05). In the ranibizumab and CTGF shRNA dual targets intervention group, the levels of CTGF and VEGF mRNA were decreased as compared to the non-intervention group (t=-6.09, -5.11;P＜0.001), which was similar to CON2 group (t=-1.16, 1.139; P＞0.05). Conclusions Both CTGF and VEGF gene expression are up-regulated in early diabetic rat retina, and the level of CTGF increased earlier than VEGF. Ranibizumab combined with CTGF shRNA could simultaneously reduce the level of CTGF and VEGF mRNA in diabetic rat retina.
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 intravitreal injection of conbercept in the treatment of retinopathy of premature (ROP) and to analyze the factors related to the therapy.MethodsA retrospective study. A total of 57 patients (57 eyes) with pre-threshold type 1 (30 patients, 30 eyes), threshold ROP (21 patients, 21 eyes) and acute aggressive posterior ROP (APROP, 6 patients, 6 eyes)) from premature infants by retinal screening in Henan Provincial People’s Hospital during October 2017 and June 2018 were enrolled in this study. All children were received routinely intravitreal injected 10 mg/ml conbercept 0.025 ml (0.25 mg) within 24 hours after diagnosis. Fundus examination was performed 7 days after injection. The interval of examination was 1?3 weeks according to fundus conditions. The mean follow-up was 30.1±4.6 weeks. For patients with relapse or no response to treatment, repeated intravitreal injection of conbercept or laser photocoagulation therapy was given. The retinal blood vessels of the affected eyes were observed. Logistic stepwise regression analysis was used for the correlation test of multiple factors.ResultsAmong 57 eyes, 49 eyes and 8 eyes were treated with 1 or 2 times of intravitreal injection of conbercept. After 24 weeks of treatment, in 57 eyes, 26 eyes were cured (45.6%), 22 eyes improved (38.6%), 8 eyes relapsed (14.0%), and 1 eye aggravated (1.8%). The recurrence time was 12.9±4.5 weeks after the first injection, and the corrected gestational age was 49.0±6.7 weeks. There were significant differences in initial injection time, lesion range among the cure, improved and recurrence eyes (F=5.124, 7.122; P＜0.01, ＜0.01). Parameters of ROP condition, including ROP diagnosis (pre-threshold type 1, threshold and APROP), zone (zone 1 and 2), stage (stage 2 and 3) and plus lesions, were significant different among the cure, improved and recurrence eyes (χ2=11.784, 14.100, 6.896, 9.935; P＜0.01, ＜0.01, ＜0.05, ＜0.01). Logistic stepwise regression analysis showed that the recurrence rate was correlated with ROP zone, more likely recurrence at zone 1 than zone 2 (Wald=9.879, OR=27.333, P=0.002). No injection-related complications such as endophthalmitis, cataract and glaucoma were found during treatment and follow-up period.ConclusionsIntravitreal injection of conbercept is effective in the treatment of ROP without obvious adverse reactions. Lesion zoning is associated with recurrence after treatment.
Objective To compare the features of OCT angiography (OCTA) between neovascular age-related macular degeneration (nAMD) and myopic choroidal neovascularization (mCNV) patients before and after intravitreal anti-VEGF treatment. Methods A prospective cohort study. Twenty-nine patients (37 eyes) with nAMD (19 males and 10 females, aged 68.20±8.76) and 31 patients (34 eyes) with mCNV (9 males and 22 females, aged 43.10±11.80, with the mean diopter of ?9.71±1.20 D) from Department of Ophthalmology, West China Hospital of Sichuan University during May and December 2017 were included in this study. Ranibizumab or Conbercept (0.5 mg/0.05 ml) was intravitreally injected in all eyes. The patients were follow-up for 3?6 months. The OCTA was conducted before treatment and 1 day, 1 week, 1 month and 3?6 months after treatment. In order to ensure that the scanning position was the same, the tracking mode was adopted for each scanning. According to the OCTA images, the lesion area, parafoveal superficial vessel density and perfusion area were measured and analyzed contrastively between nAMD and mCNV patients. Results The mean lesion area before and 1 month after treatment in nAMD patients were 0.38±1.87 mm2 and 0.06±0.12 mm2, while in mCNV patients, those were 0.26±1.06 mm2 and 0.03±0.05 mm2, respectively. There were statistically significant differences (Z=4.181, 4.475; P＜0.001) in CNV lesion area before and 1 month after treatment between nAMD and mCNV patients. Compared with those before treatment, the absolute change (Z=1.853, P=0.064) and the percentage changes (t=2.685, P=0.010) of CNV lesion area 1 month after treatment in nAMD and mCNV patients show a statistical meaning. There were significantly decreases in both parafoveal superficial vessel density (F=8.997, P=0.003) and perfusion area (F=7.887, P=0.015) 3 months after treatment in nAMD patients, while decreases in parafoveal superficial vessel density (F=11.142, P=0.004) and perfusion area (F=7.662, P=0.013) could be detected 1 day after treatment in mCNV patients, before rising 1 month after treatment. Conclusions There are significantly differences in lesion area before and after the treatment of intravitreal anti-VEGF between nAMD and mCNV patients by OCTA examination. Moreover, the changes of both parafoveal superficial vessel density and perfusion area after anti-VEGF treatment are statistically different in two groups.
Objective To investigate the effect of photodynamic therapy (PDT) combined with intravitreal bevacizumab on wet age-related macular degeneration (AMD). Methods In this retrospective study, 34 eyes (28 cases) diagnosed with wet AMD received PDT combined intravitreal injection of bevacizumab, including 25 eyes with classic CNV and 9 eyes with minimally classic CNV by fluorescein angiography; On optical coherence tomography (OCT), 23 eyes showed intraretinal fluid (IRF) and 11 eyes presented subretinal fluid (SRF). After signing informed consent, all patients underwent initial standard PDT followed by intravitreal bevacizumab (1.25 mg) within succeeding 3 to 7 days. Best corrected visual acuity (BCVA) and OCT with routine eye examinations were evaluated monthly. Additional bevacizumab (1.25 mg) was injected intravitreally if new or increasing fluid appreciated on OCT, or BCVA lowered more than 5 letters even with stabilized fluid. Injection was discontinued if no fluid was showed on OCT (quot;dry macularquot;), or BCVA was stabilized even with fluid after two consecutive injections. BCVA and central retinal thickness (CRT) were analyzed and compared between baseline and 6 month follow-up. The correlation between parameters such as baseline BCVA, greatest linear dimension (GLD), type of CNV, SRF or IRF and posttreatment BCVA will be analyzed. The injection number of bevacizumab and complications were recorded. Results Compared to baseline, BCVA improved (9.4plusmn;10.2) letters and reach 44.9plusmn;21.3 letters (t=5.438，P＜0.01) and CRT decreased (184.6plusmn;214.6) mu;m (t=4.810，P＜0.01) at 6 month visit. The average of injection number was 1.9plusmn;0.9 (including initial injection of combination therapy). With multiple lineal regression analysis, only baseline BCVA correlated to posttreatment BCVA at 6 month visit (r=0.802.P＜0.01). The type of CNV, GLD, SRF or IRF on OCT and CRT at baseline were not associated to post-treatment BCVA (r=0.053, -0.183, 0.139 and 0.053, respectively.P＞0.05). BCVA of eyes with SRF (14.7 letters) increased more than eyes with IRF (6.9 letters) on OCT (t=-2.207，P=0.035). The change of BCVA after treatment (t=-0.076), change of CRT (t=-1.028) and number of injections (Z=-1.505) were not different between classic CNV and minimally classic CNV (P＞0.05). The change of CRT (t=-0.020) and number of injections (Z=-0.237) did not present difference between SRF and IRF (P＞0.05). The change of BCVA (t=1.159) and number of injections (Z=-1.194) were not correlated to whether residual fluid or not at 6 month visit (P＞0.05). No severe complications were noticed during follow-up.Conclusion For wet AMD patients, PDT combined intravitreal bevacizumab could improve visual acuity, reduce retinal thickness and control CNV progress in a short-term.
Objective To observe the inhibitory effect of Bevacizumab on retinal neovascularization in oxygen-induced retinopathy in the mouse. Methods 90 one-week-old C57B L/6J mice were divided into four groups at random. 15 mice in the 1st group as normal control group, 15 mice in the 2nd group as oxygen control group, 30 mice in the 3rd group as high-dose Bevacizumab treatment group, 30 mice in the 4th group as low-dose Bevacizumab treatment group. The 2nd, 3rd and 4th groups were exposed to 75% oxygen for 5 days and then to room air. At the 12th day, One eye of each mouse of two control groups were received an intravitreal injection with Be vacizumab at 2 mu;l、1 mu;l respectively, and the same volume of BSS was injected into the other eye of the mice. The adenosine diphosphatase (ADPase) histochemical technique was used for retinal flat mount to assess the oxygen-induced change s of retinal vessels. The number of the endothelium cell nuclei of proliferative neovascularization was quantified by retinal microtome chromoscopy. Real-time PCR analysis was performed to examine the expression of VEGF mRNA. Results Comparing with oxygen control group, regular distributions, reduced density of retina l vascular and reduced endothelium cell nuclei which extending retinal membrane were observed in the treatment groups(P＜0.001). But the differences between two treatment groups are not statistically significant (P＞0.05). The expression of VEGF mRNA was not significantly different in oxygen control group whatever it whether accepted Bevacizumab treatment or high or low dose (P＞0.05). Conclusion Intravitreal injection with Bevacizumab can effectively inhibits the retinal neova scularization in oxygen-induced retinopathy in the mouse. Intravitreal injection with Bevacizumab might become to the new method to treat retinopathy of premature. （Chin J Ocul Fundus Dis，2008，24：184-188）
Objective To observe the clinical efficacy of intravitreal Ranibizumab on exudative agerelated macular degeneration (AMD).Methods The clinical data of 46 patients（52 eyes）with exudative AMD were analyzed retrospectively. All patients were diagnosed by examination of early treatment of diabetic retinopathy study (ETDRS) charts, color fundus photograph，fluorescein angiography（FFA）or indocyanine green angiography（ICGA）and optical coherence tomography（OCT）.They received intravitreal injection of 0.05 ml (10 mg/ml) Ranibizumab, once per month for 3 months. Further injection may be required if the monthly followup indicated. A total of 52 eyes received 214 times of injections, each eye received 2-6 injections (mean 4.12). The Followup duration was 12 months. Vision acuity, fovea thickness and CNV leakage before and after treatment were analyzed.Results At the 12th month after treatment, the mean letter of ETDRS charts was 37.80 (11.40 letters more that pretreatment index,Plt;0.01). FFA and (or) ICGA showed complete closures choroidal neovascularization (CNV) in 11 eyes（21.20%），partial closures in 34 eyes (65.40%)，no change in four eyes (7.70%)，lesion growth in two eyes（3.80%）and new lesion in one eye (1.90%).OCT indicated the average of fovea thickness was 187.50 mu;m (122.80 mu;m less than the pretreatment index, Plt;0.01).Conclusion Intravitreal injection of Ranibizumab for exudative AMD according to this therapeutic schedule was well tolerated，with an improvement in visual acuity，FFA or ICGA and OCT.
bjective To separate the SO-Rb50 cells antigen corresponding to the monoclonal antibody of anti-retinoblastoma. Methods The antigen corresponding to the monoclonal antibody of anti-retinoblastoma was separated elementarily by ion-exchange chromatography, and was identified by dot-blotting using the monoclonal antibody of anti-retinoblastoma. The target protein band of the antigen was separated in light of sodium dodecyl sulfate-polyacrylamide gelelectrophoresis. Results A special unmixed band of SO-Rb50 cells antigen was separated with the relative molecular weight of 83×103.Conclusion The antigen corresponding to the monoclonal antibody of anti-retinoblastoma could be separated from SO-Rb50cells.(Chin J Ocul Fundus Dis，2003，19：152-155)
PURPOSE:To verify existance of a-,~-,and 3'-protein kinase C(PKC)subspecies and their localization in rabbit retina. METHODS: Using an immunohistoehemical technique with mono- elonal antibodies against PKC isozymes- I (a),-I[ (13),and -~[ (Y) to characterize the distribution of PKC in rabbit retina. RESULTS:There is a positive immunostaining for a-,13-,and ~-PKC in rabbit retina. The immunoreactivity of a-PKC was observed mainly in the bipolar cells of inner nuclear layer and the outer segments of photorecptors. The positive immunostaining of 13-PKC could be seen in the ganglion cells,inner plexiform layer,inner nuclear layer,and the outer segments of photoreceptors. A diffuse and weak staining of Y-PKC is recognized in the ganglion cell layer,inner plexifrom layer,inner nuclear layer, and the outer segments of photoreceptors. CONCLUSION:The protein kinase C sub- speeies-a,-~,and-'Y are present in retina which is a part of the central nervous system