ObjectiveTo evaluate the efficacy and safety of intravitreal ranibizumab (IVR) for the treatment of retinopathy of prematurity(ROP). MethodsA total of 57 eyes of 29 premature infants with diagnosis of high-risk pre-threshold, threshold ROP, or aggressive posterior ROP were reviewed and analyzed in the study. The lesions of 18 eyes were located in zoneⅠ, 39 eyes were located in zoneⅡ. All infants in the study received IVR (10 mg/ml, 0.025 ml) as the initial treatment within 24 hours after diagnosis. Follow-up examinations were performed after treatment, every week at the first month, every 2 weeks at the second and third month, every month afterward, until vascularization of zoneⅢwas observed. Follow-up ranged from 16 weeks to 52 weeks, and the average follow-up time was (28.1±11.7) weeks. If the infants didn't respond positively to the treatment or the disease recurred, the additional treatments were applied. 36 eyes (63.2%) received a single injection, whereas 21 eyes (36.8%) received additional treatments. The follow-up examinations included the development of retinal vessels, the ocular or systemic adverse events. ResultsAmong the eyes, the development of peripheral retinal vessels could be observed in 36 eyes (63.2%) which received a single injection; clinical improvement in 11 eye (19.3%) which received repeat injection; stable disease in 10 eyes (17.5%) which received laser therapy. Among the eyes, 18 eyes (31.6%) recurred, including ggressive posterior ROP (14 eyes), threshold ROP (2 eyes) and high-risk pre-threshold ROP (2 eyes). The mean time of recurrence was (5.7±2.1) weeks (range 2.0-8.0 weeks). Three eyes (5.3%) of high-risk pre-threshold, threshold ROP lacked a positive response to the treatment. The lesions were controlled after additional laser given in these eyes. No serious ocular or systemic adverse events associated with the drug or the injection was observed during the follow-up period. ConclusionIVR is safe and effective for most ROP infants. In cases of recurrence or no response, conventional laser treatment or an additional IVR injection were needed.
ObjectiveTo compare the efficacy of photodynamic therapy (PDT) alone or in combined with ranibizumab versus ranibizumab monotherapy (intravitreal injection, IVR) in patients with polypoidal choroidal vasculopathy (PCV). Methods80 eyes of 72 patients with PCV were enrolled into this retrospective and comparative study according to their therapeutic plan. 30 eyes of 28 patients, 28 eyes of 30 patients and 22 eyes of 21 patients were divided into PDT group, ranibizumab 0.5 mg group (IVR group) or the combination group, respectively. The patients with PCV were diagnosed according to clinical symptoms, optical coherence tomography (OCT) and fluorescent indocyanine green angiography (ICGA). The baseline best-corrected visual acuity (BCVA) before treatment was more than 0.05, and there was no retinal fibrosis and scar for all patients. There was no statistical difference of age (F=0.187), gender (χ2=0.423), average BCVA (F=1.120) and central retinal thickness (CRT) (F=0.431) among three groups (P > 0.05). They had not received any treatment before. Patients received verteporfin PDT in PDT group, 3 consecutive monthly IVRs starting day 1 in IVR group, and 3 IVRs after 3 days, 1 month, 2 months of PDT starting day 1 in combination group. Re-treatment was considered 3 months later if the follow up shown no changes in fundus photography, OCT and ICGA. The average follow-up time was 19 months. BCVA at baseline and follow-up visit at 1, 3, 6, 12 months was measured, and the proportion of patients with ICGA-assessed complete regression of polyps at month 6 was recorded as primary outcome. The CRT was measured at baseline and 6 months as secondary outcome. ResultsThere were significant difference of BCVA at 1, 3, 6 and 12 months among three groups(F=5.480, 5.249, 3.222, 4.711; P < 0.05). The average BCVA was significantly better at 1, 3, 6, 12 month than that at baseline(t=-6.632, -4.127, -3.904, -4.494; P < 0.05) in combination group, and was significantly better at 3, 6, 12 months than that at baseline (t=-5.636, -3.039, -3.833; P < 0.05) in IVR group. However there was no significant difference of the average BCVA in PDT group between follow-up at 1, 3, 6, l 2 months and baseline (t=1.973, 0.102, -0.100, -0.761; P > 0.05). The proportion of patients with complete regression of polyps at 6 months was higher in PDT (76.7%) or combination group (68.2%) than IVR group (35.7%) (χ2=0.003, 0.025; P < 0.05). There was no significant difference of CRT among 3 groups at baseline (P=0.651). The mean CRT decreased in all 3 treatment groups over 6 months (t=5.120, 3.635, 5.253; P < 0.05), but there was no significant difference of CRT among 3 groups (F=1.293, P > 0.05). ConclusionsThree therapies could effectively decrease CRT. IVR or IVR combined with PDT are both more effective than PDT therapy to improve vision of PCV patients. PDT or PDT combined with IVR was superior to IVR pnly in achieving complete regression of polyps in 6 months in PCV patients.
ObjectiveTo compare the one year efficacy of intravitreal injection with ranibizumb for macular edema (ME) secondary to ischemic and non-ischemic central retinal vein occlusion (CRVO).MethodsA total of 88 patients (88 eyes) with ME secondary to CRVO were enrolled in this retrospective study. The best corrected visual acuity (BCVA) was detected by the Early Treatment Diabetic Retinopathy Study Chart. The optical coherence tomography was used to measure the foveal retinal thickness (CRT) and macular edema volume. The patients were divided into non-ischemic group and ischemic group, 44 eyes of 44 patients in each group. There was no significant differences in age (t=0.650, P=0.517) and gender (χ2=0.436, P=0.509) between the two groups. Compared with the ischemic group, the CRT was significantly decreased in the non-ischemic group (t=−2.291, P=0.024), and the edema volume in the macular area was significantly reduced (t=−2.342, P=0.022). All eyes were treated with continuous intravitreal injection of ranibizumab three times, and repeated injections were performed as needed. The patients without obvious ME regression after treatment were combined with triamcinolone acetonide injection. The patients with peripheral retinal non-perfusion area were combined with peripheral retinal laser photocoagulation. The follow-up was 1 year. The number of injections was counted. The changes of BCVA, CRT and edema volume in the macular area were compared between the two groups.ResultsDuring the 1-year follow-up period, 88 eyes were injected 1 to 10 times, with the mean of 4.51±2.33. The number of injections in the ischemic group and non-ischemic group were 4.55±1.59 and 4.48±2.91, respectively. There was no significant difference in the average number of injections between the two groups (t=0.136, P=0.892). The number of acetonide injections and laser treatment in the ischemic group was significantly higher than that in the non-ischemic group (t=3.729, 9.512; P＜0.001). At the last follow-up, compared with the ischemic group, the BCVA was increased (t=8.128), the CRT was decreased (t=−7.029) and the edema volume in the macular area was decreased (t=−7.213) in the non-ischemic group (P＜0.001).ConclusionCompared with ME secondary to ischemic CRVO, intravitreal injection of ranibizumab for ME secondary to non-ischemic CRVO has the better outcome of vision improvement and edema regression as well as less frequent of acetonide injections and laser treatment.
ObjectiveTo assess the efficacy and safety of intravitreal aflibercept injection (IAI) compared with photodynamic therapy (PDT) in the treatment of Chinese patients with predominantly classic subfoveal choroidal neovascularization (CNV) lesions secondary to neovascular age-related macular degeneration (nAMD).MethodsA randomized, double-blind, multi-center phase-3 clinical trial lasting for 52 weeks (from December 2011 to August 2014). Subjects were randomized in a 3:1 ratio to either IAI group or PDT-to-IAI group. Subjects in the IAI group received 2 mg IAI at baseline and at week 4, 8, 16, 24, 32, 40, 48, with sham injection at week 28, 36. Subjects in the PDT-to-IAI group were forced to receive PDT once at baseline and more time at week 12, 24 if PDT retreatment conditions were met. Sham injections were given in PDT-to-IAI group at baseline and at week 4, 8, 16 and 24, followed by 2 mg IAI at week 28, 32, 36, 40, 48. The primary outcome of efficacy were the change in mean Best Corrected Visual Acuity (BCVA) from baseline to week 28, and that of week 52. Safety evaluation included the percentage of subjects who suffered treatment emergent adverse events (TEAEs).ResultsAmong the 304 subjects enrolled, there were 228 and 76 cases in IAI group and PDT-to-IAI group respectively. At week 28, the changes of mean BCVA in IAI group, PDT-to-IAI group compared to baseline were +14.0, +3.9 letters, respectively. At week 52, the changes of mean BCVA in two groups were +15.2, +8.9 letters respectively with the difference of +6.2 letters (95%CI 2.6−9.9, P=0.000 9). At week 52, the mean foveal retinal thickness in the two groups decreased by −189.6, −170.0 μm, respectively. Subjects with the most BCVA increase in IAI group were those aged ＜65, and those with active CNV lesion area ＜50% of total lesion area. The most common TEAEs in IAI group and PDT-to-IAI group are macular fibrosis [11.8% (27/228), 6.6% (5/76)] and BCVA decline [6.6% (15/228), 21.1% (16/76)]. There were 3 cases of arterial thromboembolic events defined in the antiplatelet experimental collaboration group, but all were considered unrelated to interventions.ConclusionsThe efficacy of aflibercept is superior to that of PDT in nAMD patients in China. The therapeutic effect of aflibercept persisted to week 52 in all subjects. The rate of adverse events was consistent with the safety data of aflibercept known before.
According to the best corrected visual acuity and the morphological changes of the macular fovea, responses to the neovascular age-related macular degeneration (nAMD) who receive anti-vascular endothelial growth factor (VEGF) therapy show large variability, including poor and non-responders. Various factors will be reviewed to account for poor and non-response to anti-VEGF therapy, such as the related susceptibility genes, factors related with the development of choroidal neovascularization and morphologic parameters, pharmacokinetics and tachyphylaxis. The future research should focus on comprehensive assessment of factors affecting the efficacy of anti-VEGF therapy to improve the therapeutic outcome of nAMD.
ObjectiveTo further compare the effect of intravitreal injection of bevacizumab (IVB) and photodynamic therapy (PDT) for the treatment of choroidal neovascularization (CNV) secondary to pathologic myopia by meta-analysis. MethodsPertinent publications were identified through systemic searches of PubMed, EMBASE and the Cochrance Controlled Trials Register. All clinical comparative studies of IVB or PDT as initial treatment for CNV secondary to pathologic myopia were included. Meta analysis of these clinical trials was performed to analyze the effect of IVB and PDT for CNV secondary to pathologic myopia. Measurements included best corrected visual acuity (BCVA) and central foveal thickness (CFT). ResultsA total of 6 comparative studies involving 351 eyes were included. There were 196 eyes in IVB group and 215 eyes in PDT group. Funnel plots, Egger linear regression and Begg method did not show publication bias. Compared with PDT group, at 3, 6 and 12 months after IVB treatment, BCVA significantly increased . However, change of CFT at 3, 6 and 12 months did not vary significantly between IVB group and PDT group (3 months: WMD=-22.49, 95% CI=-93.49 to 48.52, P=0.53; 6 months: WMD=-17.34, 95% CI=-56.00 to 21.31, P=0.38; 12 months: WMD=-5.32, 95% CI=-56.37 to 45.74, P=0.84). ConclusionPatients with CNV secondary to pathologic myopia experienced a significant benefit of visual improvement after IVB, but reduction in CFT after the IVB or PDT did not vary significantly.
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.
ObjectiveTo observe the effect of conbercept combined with 577 nm subthreshold micropulse laser photocoagulation on diabetic macular edema (DME).MethodsA prospective randomized controlled clinical study. From June 2016 to June 2017, 68 eyes of 68 patients with DME diagnosed in Central Theater Command General Hospital were enrolled in the study. The patients were randomly assigned to two different treatment groups: 36 eyes (36 patients) in the conbercept combined with 577 nm subthreshold micropulse lase group (combined treatment group) and 32 eyes (32 patients) in conbercept group (drug treatment group). All patients received three initial intravitreous injection of conbercept and re-treatment was performed according to the criteria which has been disigned before. BCVA was measured by ETDRS charts. The central macular thickness (CMT), total macular volume (TMV) were measured by Topcon 3D-OCT 2000. The BCVA, CMT and TMV in the combined treatment group and the drug treatment group were 57.9±12.4 letters, 427.8±129.4 μm, 10.14±1.50 mm3 and 59.0±16.0 letters, 441.0 ±135.7 μm, 10.43±2.10 mm3, respectively. There was no significant difference (t=0.321, 0.410, 0.641; P=0.749, 0.683, 0.524). The follow-up period was more than 12 months. The changes of BCVA, CMT and TMV were compared between the two groups. Comparison of BCVA, CMT, TMV before and after treatment in and between groups using repeated measures analysis of variance.ResultsThe average annual injection times was 5.8±1.9 in the combined treatment group and 8.5±2.4 in the drug treatment group. The difference was statistically significant (t=5.12, P=0.000). The BCVA in the 3rd, 6th, 9th and 12th month were 64.9±11.1, 65.6±10.5, 67.0±10.8, 66.6±10.7 letters and 65.7±15.8, 66.9±15.7, 66.4±13.0, 67.3±16.4 letters, respectively, and there were significant differences compared with BCVA before treatment (F=34.234, 10.137; P=0.000, 0.000). The CMT were 335.2±105.9, 352.6±106.6, 336.2±120.8, 305.9±97.0 μm and 323.9±92.8, 325.5±90.2, 327.6±108.2, 312.2±106.8 μm, respectively. The TMV were 9.20±1.08, 9.26±1.20, 9.20±1.63, 9.05±1.18 mm3 and 9.19±1.21, 9.35±1.69, 9.09±1.20, 8.92±1.10 mm3, respectively. Compared with the CMT (F=12.152, 12.917; P=0.000, 0.000) and TMV (F=11.198, 11.008; P=0.000, 0.000) before treatment, the differences were statistically significant.ConclusionConbercept combined with 577 nm subthreshold micropulse laser and conbercept can effectively reduce CMT, TMV and improve BCVA in patients with DME, but combination therapy can reduce the injection times of conbercept.
ObjectiveTo observe the efficacy and safety of vitrectomy combined with submacular injection of tissue-type plasminogen activator (t-PA), gas filling and anti-VEGF drugs (multiple therapy) for thick submacular hemorrhage.MethodsA retrospective case study. From January 2014 to June 2018, 24 patients (24 eyes) with thick submacular hemorrhage who received multiple therapy at the Department of Ophthalmology of Peking University Third Hospital were included in the study. Among them, there were 15 males and 9 females with the average age of 69.05±8.86 years. The average submacular bleeding time was 17.15±10.30 days, the average bleeding area was 13.85±8.63 DD. Seventeen eyes showed hemorrhagic RPE detachment. The international standard visual acuity chart was used to BCVA examination, which was converted to logMAR visual acuity in statistics. The frequency domain OCT was used to measure the height of the foveal elevation. The average logMAR BCVA of the affected eye was 1.37±0.38. The average height of the macular fovea was 824.94±294.38 μm. All eyes underwent 23G or 25G vitrectomy. During the operation, 0.1-0.5 ml t-PA (10 μg/0.1 ml) was injected under the macula. The vitreous cavity was filled with 15% C3F8 after gas-liquid exchange in 13 eyes, and 11 eyes were filled with sterilized air. Eleven eyes were injected with anti-VEGF drugs at the end of the operation, and anti-VEGF drugs were given PRN treatment according to the activity of the lesion. The average follow-up time after treatment was 27.90±22.21 months. The absorption of bleeding under the macula, the improvement of vision, the occurrence of rebleeding and treatment-related complications were observed and recorded. The Wilcoxon rank sum test was performed to compare the BCVA and the height of foveal elevation before and after treatment.ResultsOne month after the treatment, the blood in the fovea of all affected eyes was cleared. At the last follow-up, the logMAR BCVA and macular foveal elevation were 0.82±0.28 and 253.88±71.75 μm, respectively. Compared with those before treatment, the difference was statistically significant (Z=－3.727, －3.234; P＜0.001, ＜0.001). The average intravitreal injection of anti-VEGF drugs was 1.08 times. During the operation, a tiny hole was formed in the center of the macula when t-PA was injected under the retina. Two eyes showed mild vitreous hemorrhage early after the operation. During the follow-up period, bleeding recurred in 2 eyes.ConclusionsVitrectomy combined with submacular injection of t-PA, gas filling, and anti-VEGF drugs is an optimal combination for the treatment of thick submacular hemorrhage. It can effectively remove submacular hemorrhage, improve vision, reduce foveal elevation with good safety.
For choroidal neovascularization (CNV) secondary to pathological myopia, intravitreal injection of anti-VEGF has been widely used in clinic and achieved good outcome. However, due to the differences in the demographic characteristics, stages of disease progression and treatment procedure of CNV, the prognosis of the disease is variable. Complete ellipsoid band, smaller baseline choroidal neovascularization and better baseline vision are important predictors of good outcome of anti-vascular endothelial growth factor treatment. Chorioretinal atrophy or complications related to pathologic myopia indicate a poor prognosis. The influence of age, race, previous photodynamic therapy and early treatment on the prognosis of treatment need to be further studied.