Objective To evaluate the efficacy and safety of intravitreal anti-vascular endothelial growth factor (VEGF) combined with photodynamic therapy (PDT) vs. photodynamic therapy for polypoidal choroidal vasculopathy (PCV).Methods A computerized search was conducted in Pubmed, OVID, Chinese Biological Medicine Database（CBM）,China National Knowledge Infrastructure （CNKI） by using key words ldquo;polypoidal choroidal vasculopathy, photodynamic therapy, intravitreal anti-VEGFrdquo; in Chinese and/or English combined with manually searching of bibliographies of pertinent articles, journals and literature reference proceedings. Randomized controlled trials (RCT) and non-RCT were collected. The search time was ranged from establishment of each database to September, 2011. The search was no 1imitation in language. The best corrected visual acuity (BCVA),resolution and recurring of lesions, decrease or complete resolution of pigment epithelial detachment （PED）,visual extinction or blindness rate,the rate of subretinal hemorrhage were analyzed by RevMan 5.0 software. Results In total, one RCT and four non-RCTs (273 patients) were included in the meta-analysis involving 148 patients in single treatment group and 125 patients in combined treatment group. The results of metaanalyses showed that there was no significant difference between two groups in the mean logarithm of minimal angle of resolution BCVA at six months ［standard mean difference=0.01, 95% confidence interval (CI): -0.12- 0.14,P=0.84］and 12 months ［standard mean difference = 0.04, 95%CI: -0.16-0.25,P=0.69 after treatment. There was no significant difference between two groups in the resolution of lesions ［odds ratio (OR)=1.38,95%CI:0.74-2.55,P=0.31］ at the months after treatment and decrease or complete resolution of PED (OR=0.67,95%CI:0.12-3.69,P=0.65) at 12 months after treatment. There was no significant difference between two groups in the recurring of lesions (OR=1.14, 95% CI:0.58-2.24,P=0.71) and lost of ge; three lines vision or blindness rate (OR=1.20, 95%CI:0.34-4.18,P=0.78) at 12 months after treatment. The rate of subretinal hemorrhage in combine treatment group was significant lower than single treatment group (OR=0.41, 95%CI:0.18 -0.94,P=0.04). Conclusions The incidence of subretinal hemorrhage occurred in patients with PCV after intravitreal anti-VEGF combined with PDT is much lower than that after single PDT.But the visual improvement, resolution of lesions and recurring of lesions of combined treatment need further studied to see if it is better than single PDT.
ObjectiveTo evaluate the effectiveness and complications associated with the use of ranibizumab in the treatment of ZoneⅠand ZoneⅡretinopathy of prematurity (ROP). MethodsData from patients of ROP who had received intravitreal ranibizumab (IVR) injections in Peking University People's Hospital for the treatment of ROP from July 2012 to December 2013 were collected. In total, 151 eyes from 85 patients (56 male and 29 female) were analyzed. The mean birth weight was (1438.6±334.5) g (range:790-2280 g), mean gestational age was (30.1±2.0) weeks (range:25-37 weeks), mean age at the time of intervention was (37.0±6.2) gestational weeks (range:32-45 weeks), mean follow-up was (4.9±3.3) months (range:1.4-20.8 months). The main outcome measures were the regression of ROP and the complications that were associated with the IVR injections. ResultsAfter receiving IVR injections, 120 eyes (79.5%) exhibited ROP regression after single injection. Twenty-six eyes (17.2%) required additional laser treatment for ROP regression after the absence of a positive response to the IVR injections. Five eyes (3%) progressed to stage 4 ROP and required vitrectomy to reattach the retinas. Fifty of 120 eyes which were regressed after single IVR had recurrence of ROP and need additional laser or additional IVR. All of the eyes (100.0%) had attached retinas after the various treatments that they received. No notable systemic complications related to the IVR injections were observed. ConclusionsIVR injection seems to be an effective and well-tolerated method to treat ZoneⅠand ZoneⅡROP. Recurrence of ROP is common and long-term follow up may be needed.
ObjectiveTo evaluate the spectral domain optical coherence tomography (SD-OCT) characteristics of polypoidal choroidal vasculopathy (PCV) and its correlation with the visual acuity after photodynamic therapy (PDT) combined with intravitreal ranibizumab. MethodsTwenty-six eyes of 26 patients with PCV diagnosed by indocyanine green angiography (ICGA) were enrolled in this study. All the patients were examined for best corrected visual acuity (BCVA), slit lamp microscope, SD-OCT, fundus fluorescein angiography (FFA) and ICGA before and 1, 3 months after treatment. The mean baseline BCVA was (31.46±16.87) letters, mean central retinal thickness (CRT) was (581.19±309.05) μm, and mean subfoveal choroidal thickness (SFCT) was (248.92±95.45) μm. Patients were divided into 2 groups according to the final visual improvement after 6 month of treatment: GR or sensitive Group (17 eyes) and PR or non-sensitive Group (9 eyes). GR group included 12 males and 5 females, with a mean age of (65.24±7.03) years, a mean CRT of (619.06±335.07) μm and a mean SFCT of (271.24±106.61) μm. There were 4 eyes with subretinal hemorrhage (SRH), 2 eyes with interface retinal fluid (IRF), 13 eyes with subretinal fluids (SRF) and 15 eyes with pigment epithelial detachment (PED). PR group included 8 males and 1female, with a mean age of (64.00±7.02) years, a mean CRT of (509.67±255.21) μm and a mean SFCT of (271.24±106.61) μm. There were 6 eyes with subretinal hemorrhage (SRH), 5 eyes with interface retinal fluid (IRF), 6 eyes with subretinal fluids (SRF) and 8 eyes with pigment epithelial detachment (PED). The difference of sex, age, CRT and SFCT between these two groups was not significant (P>0.05). The relationship of baseline SD-OCT and post-treatment BCVA was analyzed. ResultsOn 1, 2, 3, 6 months after treatment, the BCVA were (38.46±19.81), (40.04±20.80), (42.96±21.63), (43.77±20.91) letters respectively. On 6 months after treatment, the mean CRT in GR and PR group were (360.71±276.54), (341.44±193.68) μm respectively (P>0.05). 64.71% (11/17) eyes in GR group and 22.22% (2/9) eyes in PR group had a SFCT thicker than 263μm. The difference was statistical significant between two groups [odds ratio (OR):0.052, 95% confidence interval (CI):0.005-0.533; P=0.013]. Logistic regression analysis showed that existence of IRF (OR=9.375, 95% CI: 1.299-67.645; P=0.026) or SRH (OR=6.500, 95% CI: 1.094-38.633; P=0.040) at baseline was negative prognostic factor to treatment. ConclusionThick SFCT is a protective factor, however, existence of IRF or SRH at baseline is negative prognostic factor of final visual improvement.
ObjectiveTo investigate the efficacy of laser photocoagulation and intravitreal ranibizumab treatment of retinopathy of premature(ROP). MethodsThis study included 49 ROP infants (96 eyes), including type 1 pre-threshold ROP (7 infants, 14 eyes), threshold ROP (38 infants, 44 eyes) and aggressive posterior ROP (AP-ROP, 4 infants, 8 eyes). According to the treatments received, all patients were divided into laser photocoagulation (LP) group (40 infants, 78 eyes) and intravitreal ranibizumab (IVR) treatment group (9 infants, 18 eyes). Generally, zoneⅡand stage 3 ROP with clear refractive media received laser photocoagulation, zoneⅠROP and AP-ROP, or eyes with unclear refractive media or infants with poor general condition received IVR. The infant gestational age, birth weight, corrected gestational age at first treatment and the cure rate of the first treatment were analyzed between the two groups, and between three disease types (type 1 pre-threshold, threshold and AP-ROP). ResultsThe gestational age and birth weight was no difference between the LP group and IVR group (t=0.827, 1.911; P > 0.05). The corrected gestational age at first treatment of LP group was significantly smaller than that in the IVR group (t=3.041, P < 0.05). In the LP group, 75 of 78 eyes (96.15%) was cured by the first treatment, 3 of 78 eyes (3.85%) progressed to stage 4A after the first treatment and was controlled by vitrectomy. In the IVR group, 8 of 18 eyes (44.44%) was cured by the first treatment, 10 of 18 eyes (55.56%) progressed to next stage after the first treatment and was controlled by additional laser photocoagulation or repeated IVR. The gestational age and birth weight was no difference between type 1 pre-threshold, threshold and AP-ROP infants (t=2.071, 0.664; P > 0.05). The corrected gestational age at first treatment of type 1 pre-threshold infants was the same of the threshold lesion infants (t=2.054, P > 0.05). The corrected gestational age at first treatment of AP-ROP infants was significantly smaller than that of type 1 pre-threshold and threshold lesion infants (t=3.250, P < 0.05). The cure rate was statistically significant (χ2=24.787, P < 0.05) between there three ROP lesions. ConclusionIVR treatment is suitable for zoneⅠlesions, AP-ROP and Plus lesions, while laser photocoagulation is appropriate for zoneⅡlesions with fibrosis and less vascular proliferation.
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.
Objective To observe the efficacy and safety of intravitreal injection of Ranibizumab(Lucentis) on exudative age－related macular degeneration (AMD). Methods To analyze retrospectively the clinical data of 56 patients with exudative AMD, which was diagnosed by examination of ETDRS charts, color fundus photograph, fluorescein angiography(FFA) or indocyanine green angiography(ICGA) and optical coherence tomography(OCT), were underwent intravitreal injection Lucentis 0.5 mg. Before the treatment, the ETDRS charts letter of 56 eyes was 25.1; choroidal neovascularization(CNA) was leaky which examined by FFA and ICGA; the average thickness of retina was 303.45 mu;m. Ranibizumab injection therapeutic times were 2.8, the average therapeutic times were 3.1. Follow－up time was 6－12 months (mean 8.7 months). Visual acuity (ETDRS charts letter), retinal thickness, leakage of CNV and operative complications before and after the treatment were analyzed. Results At the end of the follow－up period, the mean letter of ETDRS charts was 38.5, increased 13.4 letters (P＜0.01), the ETDRS charts improved 15 or more letters in 22 eyes (39.3%), decreased more than 15 letters in 2 eyes (3.6%); the foveal thickness on OCT images were 303.45 mu;m before treatment and 191.35 mu;m a fter treatment, decreased significantly (P＜0.00); FFA and/ or ICGA showed CNV complete closure in 12 eyes (21.4%), partial closure in 33 eyes (58.9%), no change in 9 eyes (16.1%) and new CNV in 1 eye (1.8%); Slight complications after operation disappeared during one week. Conclusion Intravitreal injection of Ranibizumab for exudative AMD was well tolerated, with an improvement in VA, FFA or ICGA , and OCT. (Chin J Ocul Fundus Dis,2008,24:160-163)
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 investigate the effects and safety of intravitreous injection of Conbercept combined with laser photocoagulation for macular edema secondary to branch retinal vein occlusion. MethodsAll subjects were assigned randomly to 3 groups:intravitreal Conbercept combined with laser photocoagulation group (CL group), intravitreal triamcinolone combined with laser photocoagulation group (TL group), and photocoagulation group (L group). The best-corrected visual acuity (BCVA), central macular thickness (CMT), fundus oculi and fundus fluorescein angiography (FFA), intraocular pressure (IOP), slit lamp were observed before and 1 day, 1 week, 1 month, 3 months after treatment. The changes of post-treatment BCVA and CMT in pre-therapy and post-treatment were compared, and related complications were recorded. ResultsThere were significant differences of BCVA (χ2=9.754, 12.430, 17.424, 13.189) and CMT (F=10.614, 4.099, 4.927, 8.99) between 3 groups in post-treatment 1 day, 1 week, 1 month and 3 months. The numbers of subjects of improving and stabilizing BCVA in CL group were remarkably more than that in L group in every post-treatment follow-up time (P < 0.01), whereas the CMTs in CL group were significantly less than that in L group in every post-treatment follow-up time (P < 0.05). The CMTs in post-treatment 1 day, 1 week, 1 month, 3 months were thinner than that in pretreatment in CL group and TL group (P < 0.05). Meanwhile, there was no significant difference (P > 0.05)between any two CMTs in post-treatment 1 day, 1 week, 1 month and 3 months in CL group. Yet, the CMT in post-treatment 3 months was thicker than those in post-treatment 1 day, 1 week and 1 month in TL group(P < 0.05). And there was no significant difference(P > 0.05)between any two CMTs in post-treatment 1 day, 1 week and 1 month in TL group. There was no conspicuous difference in CMTs(P > 0.05)between in CL group and in TL group in every viewing time, except for that in post-treatment 3 months(P < 0.05). There was only 1 case of intraocular hypertension in post-treatment in TL group. ConclusionsIntravitreous injection of Conbercept combined with laser photocoagulation for macular edema secondary to BRVO is effective, safe, and superior to laser photocoagulation only. Also it had a longer effective duration and less complications than intravitreal triamcinolone combined with laser photocoagulation.
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 investigate the influence of vascular endothelial growth factor (VEGF) antagonist bevacizumab on the growth of human choroidal melanoma (CM) OCM-1 cell xenografts in nude mice, and to explore the probable mechanism.Methods OCM-1 cells were subcutaneously implanted on 18 nude mice to establish ectopic model of human CM. The nude mice with the tumor of 5 mm in diameter were randomly divided into three groups: untreated group (group A), normal saline （NS） group (group B), drug treated group (group C). Bevacizumab was intraperitoneally injected for 14 consecutive days in group C, and the same volume of NS was used at a same way in group B. The volume and weight of implanted tumor as well as inhibitory rates of drug on tumor were calculated, ki67 and survivin proteins were measured with immunohistochemistry, and the mRNA expression of VEGF and survivin were assessed by RT-PCR.Results The volume and weight of tumor was (598.86plusmn;321.81) mm3, (0.66plusmn;0.15) g; (1 715.15plusmn;278.16) mm3, (1.54plusmn;0.39) g and (1 750.23plusmn;206.36) mm3, (1.54plusmn;0.31) g in groups C, A and B, respectively. There were significant differences between group C and A (F=34.53, P=0.00) and group C and group B (F=8.69, P=0.01). The inhibitory rate of these three groups were 57.14%, 5.31%, 6.25%, respectively, and the proliferation index (PI) of ki67 in these three groups were (51.85plusmn;1.32)%, (46.30plusmn;1.39)%, (27.90plusmn;0.90)%, respectively, there were significant differences in ki67 PI between C group and A or B group (H=15.17, P=0.00). The expression of survivin mRNA was (0.49plusmn;0.02), (0.82plusmn;0.05) and (0.61plusmn;0.05) in groupss C, A and B, respectively, there were significant differences between C group and A or B group (F=15.17, P＜0.05) . The expression of VEGF mRNA was (0.32plusmn;0.08), (0.73plusmn;0.07), (0.80plusmn;0.04) in groups C, A and B, significant difference was found between group C and A or B group (F=12.05，P＜0.05). Conclusion Bevacizumab can inhibit the growth of human CM in nude mice probably by inhibiting the activity of VEGF and downregulating survivin expression of the tumor as well as inhibiting the growth of the tumor.