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 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.
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 study changes in choroidal thickness(CT) with intravitreal injections of ranibizumab treatment. MethodsThis is a prospective, uncontrolled, open-label study. A total of 31 eyes of 31 patients diagnosed with wet age-related macular degeneration (AMD) and 33 eyes of 33 patients diagnosed with choroidal neovascularization (CNV) secondary to pathological myopia (PM) were included in the study. All affected eyes were treated with intravitreal ranibizumab 0.05 ml (10 mg/ml) and followed up monthly until 6 months. Enhanced depth imaging on Cirrus spectral-domain optical coherence tomography was used to measure the CT. The initial CT was compared with the data at 1, 3 and 6 month after treatment, and the correlation between of the decrease of CT at the 6 month and the number of injection times was analyzed. ResultsIn AMD group, the average CT respectively decreased by (9.68±11.02), (12.58±11.04), (13.84±11.67)μm at 1, 3 and 6 month, and the differences were significant(t=4.89, 6.34, 6.60;P < 0.001). In PM group, the average CT respectively decreased by (2.06±10.92), (3.64±8.78), (3.27±7.20)μm at 1, 3 and 6 month. The difference at 1 month was not significant (t=1.08, P=0.287). While after 3 months and 6 months, the differences were significant(t=2.38, 2.61;P=0.024, 0.014). The injection times were not correlated with the CT decreases at 6 month in both groups(r=0.04, 0.30;P=0.815, 0.099). ConclusionIntravitreal injections of ranibizumab can induce choroidal thickness reduction for wet age-related macular degeneration and choroidal neovascularization secondary to pathologic myopia.
Intravitreal injection of antiangiogenic agents is widely used to treat retinal vascular disease. This therapy can induce regression of neovascular vessels; reduce intraocular inflammation and retinal vascular permeability, and control macular edema. However the action period of these agents is short, and thus this therapy need repeated injections which cause higher operation risk and cost. Retinal laser photocoagulation therapy can close retinal capillary non-perfusion area and neovascular vessels, reduce macular edema caused by vascular leakage. However, as its therapeutic effect is based on the destruction of the retinal tissues in the lesion area, this therapy need longer time to show its effects. When the disease is controlled by this method, it may already induce some structural irreversible damages to the retina, especially the macular. This is why the visual acuity is not satisfactory in some patients, even though the disease get controlled, macular edema gets disappeared and anatomical structure of retina get improved. Properly evaluating all the pros and cons of retinal photocoagulation and intravitreal injection of antiangiogenic agents, will allow us to explore a better way to combine these two therapies to treat retinal vascular diseases.