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.
In the expert consensus published by the Pediatrics in 2013, it was first proposed that anti-VEGF drugs can be considered for retinopathy of prematurity (ROP) with stage 3, zone Ⅰ with plus disease. However, there are many problems worth the attention of ophthalmologists, including the advantages and disadvantages of anti-VEGF therapy compared with traditional laser therapy, systemic and ocular complications after anti-VEGF therapy, and what indicators are the end points of anti-VEGF therapy. Combined with this consensus and numerous research findings, we recommend that the first treatment for anti-VEGF or laser therapy should be considered from disease control effects. For the threshold and pre-threshold lesions, the effect of anti-VEGF therapy for zoneⅡ lesions is better than that for zone Ⅰ lesions and the single-time effective rate is high. So, it is suggested that anti-VEGF therapy should be preferred for the first treatment. The choice of repeat treatment should be considered from the final retinal structure and functional prognosis. Laser therapy is advisable for the abnormal vascular regression slower and abnormalities in the posterior pole. It can reduce the number of reexaminations and prolong the interval between re-examinations. However, the premature use of laser has an inevitable effect on peripheral vision field. Excluding the above problems, supplemental therapy can still choose anti-VEGF therapy again. Most of the children with twice anti-VEGF therapy are sufficient to control the disease. Anti-VEGF therapy should be terminated when there are signs such as plus regression, threshold or pre-threshold lesions controlled without recurrence, peripheral vascularization, etc.
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 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.
ObjectiveTo study the changes the changes of cytokine expression the aqueous humor of patients with macular edema secondary to branch retinal vein occlusion (BRVO-ME) before and after intravitreal ranibizumab (IVR). MethodsA prospective clinical study. From June 2018 to June 2021, 31 eyes of 31 patients with non-ischemic BRVO-ME diagnosed by ophthalmic examination in Department of Ophthalmology, Beijing Hepingli Hospital were included in the study. Among them, 15 males had 15 eyes, and 16 females had 16 eyes. Age was 70 (65, 72) years; the course of disease was 10 (9, 15) days. All of them were first-time patients. All eyes were treated with IVR once a month for 3 consecutive months. At the end of each IVR treatment, 0.1 ml aqueous humor was extracted immediately. The concentrations of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in aqueous humor were detected by flow cytometry. The concentrations of cytokines in aqueous humor before and after treatment were compared by Kruskal-Wallis or Wilcoxon signed-rank test. Spearman correlation analysis was performed on the correlation between VEGF and MCP-1 expression level in aqueous humor before treatment. ResultsThe concentrations of VEGF and ICAM-1 in aqueous humor were significantly lower at 1 month after treatment compared with that before treatment, and at 2 months after treatment compared with that at 1 month after treatment (Z=4.03, 3.25, 2.50, 3.48; P＜0.05); the concentrations of IL-6 and VCAM-1 increased and the concentration of MCP-1 decreased, but there was no significant difference (Z=－0.21, 1.42, 0.86, －0.53, 0.92, －1.57; P＞0.05). Spearman correlation analysis showed that there was a strong positive correlation between VEGF and MCP-1 in aqueous humor before treatment (r=0.78, P＜0.001). ConclusionThe concentrations of VEGF and ICAM-1 in aqueous humor significantly decrease after IVR treatment in BRVO-ME; the concentrations of IL-6, MCP-1 and VCAM-1 do not obviously change.
ObjectiveTo study the changes and correlation of cytokines in aqueous humor before and after intravitreal injection of conbercept (IVC) treatment in patients with proliferative diabetic retinopathy (PDR).MethodsA prospective clinical study. From March to December 2019, 36 patients (42 eyes) of PDR patients treated with IVC combined with pars plana vitrectomy (PPV) (the observation group) and 27 patients (31 eyes) underwent cataract surgery in the same period (control group) in Department of Ophthalmology of the First Affiliated Hospital of Guangzhou University of Chinese Medicine were included in this study. Before PPV 5-7 days, IVC treatment was performed, and the aqueous humor were extracted during IVC and second-stage PPV in the observation group. The aqueous humor was extracted during cataract surgery in the control group. Luminex assay was used to detect VEGF-A, placental growth factor (PLGF), platelet-derived growth factor-AA (PDGF-AA), platelet-derived growth factor-BB (PDGF-BB), angiopoietin-like protein 4 (ANGPTL4), IL-6, IL-8, IL-1β, monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α) cytokine expression. For normally distributed data, the independent sample t test was used for comparison between two independent samples; for non-normally distributed data, the Wilcoxon rank sum test was used for comparison between two independent samples. The correlation analysis used Spearman rank correlation test.ResultsBefore IVC treatment, the concentrations of VEGF-A, PLGF, PDGF-AA, ANGPTL4, IL-6, IL-8, MCP-1 and ICAM-1 in the aqueous humor of PDR patients were significantly higher than those in the control group (P＜0.05). After IVC treatment, the concentration of VEGF-A in the aqueous humor was significantly lower than that before treatment, and the concentrations of ANGPTL4 and IL-8 were significantly higher than those before treatment (P＜0.05). There were no significant differences in the concentrations of PLGF, PDGF-AA, PDGF-BB, IL-6, IL-1β, MCP-1, ICAM-1 and TNF-α before and after IVC treatment (P＞0.05). Before IVC treatment, the concentration of VEGF-A was positively correlated with PLGF, PDGF-AA, PDGF-BB, ANGPTL4, IL-6, IL-8, MCP-1 and TNF-α (P＜0.05).ConclusionsIVC treatment can reduce the concentration of VEGF-A and increase the concentrations of ANGPTL4 and IL-8 in aqueous humor in PDR patients before PPV.