ObjectiveTo observe the inhibitory effect of endostatin (ES) on oxygen-induced retinal neovascularization.MethodsThirtyfour 7-day-old C57BL/6J mice were randomly divided into 3 groups: oxygen-exposed group (12 mice), ES group (12 mice) and the control group (8 mice). The mice in oxygen-exposed and ES group were exposed to (75±5)％ oxygen for 5 days and then back to the normal air. In ES group, 1 μg ES endostatin were injected into vitreous in one eye, while PBS was injected into the other eye as the control 12 and 36 hours after being exposed to oxygen. The mice in the control group were fed in normal circumstance. The changes of retinal neovascularization was examined by fluorescence angiography with fluorescein isothiocyanatedextran. The number of endothelial cells breaking through the internal limiting membrane (ILM) was counted and the inhibitory effects of ES on retinal neovascularization was observed.ResultsCompared with the oxygen-exposed group, the branches of retinal vessels went normal without any un-perfused area in ES group. The number of nuclei of endothelial cells breaking through ILM on each retinal crosssection decreased to (5.39±1.52), which differed much from that in the oxygen-exposed group (22.56±2.13) (plt;0.001).ConclusionES can effectively inhibit the formation of retinal neovascularization in rats and might be a new path of the treatment for proliferative retinopathy.(Chin J Ocul Fundus Dis, 2005,21:314-317)
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 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.
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.
Pharmaceutical therapy, including anti-vascular endothelial growth factor treatment and intravitreal corticosteroids, is the most common treatment for branch retinal vein occlusion (BRVO) and its complications, however there are confusing ideas about the protocol, patient selection, timing and endpoint of this treatment. The disease is easy to relapse with these drugs therapy. Collateral vessel formation was found in patients receiving intravitreal injection of ranibizumab or triamcinolone for BRVO and secondary macular edema. The mechanism of collateral vessel formation has not been carefully investigated. In the past thrombolysis, arteriovenous fasciostomy and laser choroidal retinal vascular anastomosis were used to reconstruct the retinal circulation, but their rationality, effectiveness and safety need to be further were studied. In recent years, because of the key technology is still immature, the artificial vascular bypass surgery experiment is not yet practical, but provides us a new idea worth looking forward to for the treatment of BRVO.
ObjectiveTo investigate the efficacy and safety of intravitreal ranibizumab and (or) triamcinolone combined with laser photocoagulation for macular edema secondary to branch retinal vein occlusion (BRVO) during one year period. MethodsThe data of 31 eyes from 31 consecutive patients with macular edema secondary to BRVO during one year follow-up visit were retrospectively analyzed. Mean best corrected visual acuity (BCVA) logMAR was (0.74±0.36) and mean central retinal thickness (CRT) was (484.48±164.81)μm at baseline. All patients received standardized clinical comprehensive examinations including vision, intraocular pressure and optical coherence tomography for diagnosis before treatment. All patients received intravitreal injections of 0.5 mg ranibizumab (0.05 ml) at first visit. The continue PRN treatment were based on the visual acuity changes and the optical coherence tomography findings. Eyes received combined triamcinolone acetonide 0.05 ml (40 mg/ml) and ranibizumab for macular edema recurrence after two injections of ranibizumab and received laser photocoagulation during 10-14 days after third injections of ranibizumab. Mean injection of ranibizumab was 3.52±2.01, 15 eyes with triamcinolone acetonide (0.84±1.21), 21 eyes with laser photocoagulation (0.97±0.95) and 12 eyes with three treatment. Compared the visual acuities and CRTs of the first and the last visits by statistical analysis. ResultsMean visual acuity improved significantly to 0.42±0.33 logMAR (t=6.611, P=0.000). Mean improvement of visual acuity was 2.90±3.07 lines. A gain of three or more logarithmic lines was evaluated in 20/31 eyes (64.52%) at the last visit. Mean CRT was (326.19±117.80)μm (t=4.514, P=0.000).Mean reduction of CRT was (333.58±134.17)μm. A decrease of 100μm of CRT was evaluated in 17/31 eyes (54.84%). No severe ocular and systematic side effect was found. ConclusionThe efficacy and safety of intravitreal ranibizumab and (or) triamcinolone combined with laser photocoagulation for macular edema secondary to BRVO were assured.
ObjectiveTo observe the efficacy of different administration of conbercept on choroidal neovasculature (CNV) in patients with pathological myopia (PM).MethodsA retrospective case-control study. From June 2012 to June 2017, 57 patients (61 eyes) with PM-CNV diagnosed in the Ophthalmology Department of General Hospital of Central Theater Command were included in this study. All patients underwent BCVA, intraocular pressure, refractive index, slit lamp microscope, FFA, OCT examination and axial length (AL) measurement. An international standard vision chart was used in the BCVA test, which was converted to logMAR vision. According to the initial treatment plan, the patients were divided into 1+PRN treatment group (group A) and 3+PRN treatment group (group B), with 27 patients (31 eyes) and 30 patients (30 eyes), respectively. There was no significantly statistical difference in baseline data between the two groups (P＞0.05). The eyes was injected with 10 mg/ml of conbercept 0.05 ml (including conbercept 0.5 mg). After completion of initial treatment, on-demand treatment was performed according to repeated treatment standards. The average follow-up time was 30.8 months. The time point for curative effect determination was 24 months after treatment. The frequency and recurrence rate of vitreous cavity injections in the two groups of patients and the changes of BCVA, central macular thickness (CMT), diopter and AL were compared and observed. Continuous variables were compared between groups by independent sample t test. Categorical variables were compared by χ2 test. logMAR BCVA and injection frequency were compared by Wilcoxon rank test. Comparison of CMT before and after treatment was performed by paired t test.ResultsAfter 24 months, the number of intravitreal injections in group A and group B were 3.94±1.88 and 4.83±1.72, respectively, with statistically significant difference (Z=－2.182, P=0.029). After completion of initial treatment, the number of retreatments in group A and group B were 2.94±1.88 and 1.83±1.72, respectively, with significantly statistical different (Z=－2.330, P=0.020). The CNV recurrence rates were 38.71% and 13.33%, respectively, with statistically significant difference (χ2=5.074, P=0.024). Compared with prior treatment, the average BCVA at 1, 3, 6, 12, and 24 months after treatment significantly increased in group A and B (Group A: Z=5.634, 5.367, 5.532, 6.344, 6.135l; P＜0.05. Group B: Z=5.809, 5.090, 5.341, 5.939, 8.103; P＜0.05). At 1, 3, 6, and 12 months after treatment, there was no statistically significant difference in the average BCVA of the two groups (Z=－0.966, －0.932, －0.523, －1.759; P=0.334, 0.351, 0.601,0.079); the difference was statistically significant at 24 months (Z=－2.525, P=0.012). Compared with CMT before treatment, the difference in the average CMT reduction of the eyes in groups A and B was statistically significant at 1, 3, 6, 12, and 24 months (Group A: t=4.691, 2.624, 2.121, 1.921, 2.237; P＜0.05. Group B: t=4.947, 4.554, 5.290, 5.567, 5.314; P＜0.05); the average CMT comparison between the two groups was not statistically significant (P=0.457, 0.871, 0.505, 0.333, 0.798). During the follow-up period, there were no ocular complications and systemic adverse reactions.ConclusionsDifferent administration methods for the treatment of PM-CNV by intravitreal injection of conbercept are safe and effective, which can effectively improve BCVA and reduce CMT. Total injection of 3+PRN is more than 1+PRN. However, the injections of retreatment and CNV recurrence rate is lower, and the final follow-up vision is better.