ObjectiveTo observe the expression of vascular endothelial growth factor (VEGF), fibrogenic mediators and inflammatory mediators in the retinal pigment epithelium (RPE)-choroid complex of mice with experimental subretinal fibrosis. MethodsBy subretinal injection of inflammatory macrophages after retinal photocoagulation, experimental subretinal fibrosis was induced in 64 adult C57BL/6(B6) female mice (7-8 weeks). Masson staining and glial fibrillary acidic protein (GFAP) staining of choroidal wholemont were performed to verify that the subretinal fibrosis at day 7 after subretinal injection. Before subretinal injection and at day 1, 2, 3, 5 and 7 after subretinal injection, the mRNA expression level of VEGF, transforming growth factor (TGF)-β1, TGF-β2, TGF-β3, interleukin (IL)-6, IL-10 and IL-13 in RPE-choroid complex were evaluated by quantitative reverse transcription-polymerase chain reaction. Enzyme-linked immune sorbent assay was next used to detect protein expression of these factors. ResultsAt seven days after subretinal injection of inflammatory macrophages, experimental subretinal fibrosis was detected by Masson staining and GFAP staining. The mRNA level of VEGF, TGF-β1 and TGF-β2 reached the peak at day 5 after modeling, while the mRNA expression of IL-6, IL-10, IL-13 reached the peak at day 2 after modeling. TGF-β3 mRNA was not detected either in naive mice or during the development of experimental subretinal fibrosis. At day 2, 3, 5 and 7 after modeling, compared with the pre-modeling, the mRNA expression of VEGF (t=2.38, 3.65, 4.03, 2.26), TGF-β1 (t=2.58, 2.30, 3.89, 4.15) and TGF-β2 (t=4.37, 4.20, 3.77, 3.98) were significantly increased (P < 0.05). At day 1, 2 and 3 after modeling, compared with the pre-modeling, the mRNA expression of IL-6 were significantly increased (t=2.36, 4.54, 4.01; P < 0.05). At day 2 and 3 after modeling, compared with the pre-modeling, the mRNA expression of IL-10 and IL-13 were significantly increased (t=3.87, 4.20, 2.44, 2.58; P < 0.05). At day 5 after modeling, compared with the pre-modeling, the protein expression of VEGF, total TGF-β1, active TGF-β1, total TGF-β2 and active TGF-β2 were significantly increased (t=2.57, 3.37, 2.45, 3.83, 2.74; P < 0.05). IL-6, IL-10 and IL-13 protein were not detected at pre-modeling eyeballs, but were found at day 2 after modeling. ConclusionThe expression of VEGF, fibrogenic mediators and inflammatory mediators in RPE-choroid complex in mice with experimental subretinal fibrosis are increase significantly.
ObjectiveTo observe the clinical efficiency of intravitreal Conbercept on exudative age-related macular degeneration (eAMD). MethodsThis is an open and prospective study without control trial. Twenty eyes from 20 patients (19 males and 1 female) with eAMD diagnosed by fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were enrolled in this study. Before the injection, best-corrected visual acuity (BCVA) of early treatment of diabetic retinopathy study (ETDRS), non-contact tonometer, ophthalmoscope, fundus photography, fundus fluorescein angiograph (FFA), indocyanine green angiography (ICGA) and optical coherence tomography (OCT) were examined. The initial average letters of ETDRS acuity were 41.20±22.61, range from 8 to 80. The initial average central retina thickness (CRT) was (345.25±131.96) μm, range from 152 to 770 μm.All affected eyes were treated with intravitreal conbercept 0.05 ml (10 mg/ml). The patients were followed up for 6 to 9 months, with the mean time of (7.35±0.99) months.The BCVA, CRT after treatment were compared with baseline using paired t-test. ResultsDuring the 1, 3, 6, 12 months after treatment and the latest follow up, the mean BCVA were all improved with statistically significant difference (t=5.85, 7.09, 7.44, 7.25; P < 0.05). At 1 month ater treatment, the mean BCVA was obviously improved in 6 eyes (30%), improved in 8 eyes (40%), stable in 6 eyes (30%). At latest follow up, the mean BCVA was obviously improved in 6 eyes (30%), improved in 9 eyes (45%), stable in 5 eyes (25%). During the 1, 3, 6, 12 months after treatment and the latest follow up, the mean CRT were all decreased with statistically significant difference (t=3.34, 3.78, 3.47, 3.44; P < 0.05). At latest follow up, the leakage in macula lutea disappeared in 6 eyes (30%), decreased in 11 eyes (55%) and increased in 3 eyes (15%). No adverse events such as secondary retinal detachment or endoophthalmitis were found during the follow-up duration. ConclusionIntravitreal conbercept is a safe and effective approach for eAMD, may improve visual acuity, exudation and macular edema.
Choroidal neovascularization (CNV) is the key characteristic of neovascular age-related macular degeneration (nAMD), and the effective therapy is intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents based on clinical and basic research. In the meantime the challenge is how to further improve the inhibiting effect for CNV and visual function of anti-VEGF treatment on nAMD. The new strategy and drug delivery devices for anti-VEGF treatment will optimize the clinical scheme. From bench to bedside, the research on targeted treatment of angiogenesis brings the bloom of nAMD medical therapy.
The therapeutic effect of anti-vascular endothelial growth factor (VEGF) for neovascular age-related macular degeneration (nAMD) was determined by a number of factors. Comprehensive thorough analysis of clinical features, imaging results and treatment response can predict the potential efficacy and possible vision recovery for the patient, and also can optimize the treatment regime to make a personalized therapy plan. Precise medicine with data from genomics, proteomics and metabolomics study will provide more objective and accurate biology basis for individual precise treatment. The future research should focus on comprehensive assessment of factors affecting the efficacy of anti-VEGF therapy, to achieve individualized precise diagnosis and treatment, to improve the therapeutic outcome of nAMD.
Objective To investigate the correlation between the vitreomacular adhesion (VMA) and exudative age-related macular degeneration (AMD). Methods A literature research was performed in PubMed, EMbase, Cochrane Library, CNKI and Wanfang database from January 2000 to December 2016. Case-control studies on the relationship between VMA or posterior vitreous detachment and exudative AMD were included in this analysis. Literature screening and data extraction were performed according to inclusion and exclusion criteria. The qualities of the literatures were evaluated according to the Newcastle-Ottawa Scale (NOS). Seven literatures were selected into meta-analysis. The NOS score was 9 points in 1 article, 8 scores in 4 articles, 7 points in 2 articles. A total of 947 eyes with exudative AMD, 638 eyes with dry AMD, and 618 eyes with controls were included. The correlation between exudative AMD and VMA were analyzed using the software Review manager 5.3. Results The prevalence of VMA in exudative AMD eyes was higher than that in controls [odds ratio (OR)=2.14, 95% confidence interval (CI)=1.19 - 3.84, P=0.010] and dry AMD eyes (OR=2.24, 95%CI=1.24 - 4.03, P=0.007). There was no difference in PVD prevalence among exudative AMD eyes, dry AMD eyes (OR=0.44, 95%CI=0.16 - 1.20, P=0.110) and controls (OR=0.70, 95%CI=0.41 - 1.18, P=0.180). Conclusion There is correlation between VMA and exudative AMD.
Exudative or wet age-related macular degeneration (AMD) is characterized by the progressive growth of choroidal neovascularization (CNV). Anti-vascular endothelial growth factor (VEGF) drugs have been used in the control of the development of CNV and vision improvement, but there are still defects like frequent injections, drug resistance and so on. Radiotherapy can deactivate local inflammatory cell populations, and make CNV unstable in the absence of pericytes and VEGF stimulation, which induce apoptosis of the vascular endothelial cells. Therefore, radiotherapy is considered as a potential adjuvant treatment of anti-VEGF therapy. The current clinical approaches include epimacular brachytherapy (EMBT) and long-range stereotactic radiotherapy (SRT). SRT may be a preferred adjuvant treatment for patients receiving anti-VEGF therapy. Knowing the progress of radiotherapy for the treatment of exudative AMD may help us to fully understand the pathogenesis of wAMD in China
Anti-vascular endothelial growth factor (VEGF) drugs, including monoclonal antibodies (such as bevacizumab and ranibizumab) and fusion protein agents (such as aflibercept and conbercept) have been clinically proven to be effective to treat exudative age-related macular degeneration AMD). However, there are still some patients do not or poorly respond to the initial anti-VEGF agents, usually after several injections, ophthalmologists may switch to another anti-VEGF agent. In general, switching of anti-VEGF agent is considered for recurrent AMD, AMD resistance to anti-VEGF treatments. Current switching protocols include the replacement of monoclonal antibodies with fusion protein agents, the replacement of fusion protein agents with monoclonal antibodies, the substitution of one monoclonal antibody with another one, and the replacement of monoclonal antibodies with fusion protein agents and switching back with monoclonal antibodies. However, current researches on the switching of anti-VEGF drugs for exudative AMD are mostly retrospective and single-arm studies, and there are some differences in the results of different studies. Therefore, for patients with exudative AMD who do not respond to or respond poorly to anti-VEGF drugs, the efficacy of switching of anti-VEGF drugs is uncertain right now. Switching of anti-VEGF agents may improve the retinal anatomical outcome of the affected eye but may not necessarily improve visual acuity. Thus it is an option in the clinical practice to treat AMD. To determine the benefits of above mentioned switching regimens, randomized controlled clinical trials with large sample number and long study period will be needed.
ObjectiveTo observe the effects of repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs on vitreous macular interface (VMI) in patients with exudative age-related macular degeneration (AMD).MethodsRetrospective study. Thirty-four exudative AMD patients who treated with intravitreal anti-VEGF drugs were included in this study. There were 26 males and 8 females. The age ranged from 50 to 80 years, with the average of (62.8±8.35) years. The eyes with at least 6 treatments during the 1-year follow-up were taken as the study eyes, and the eyes with no anti-VEGF drug treatment were the control eyes. Optical coherence tomography (OCT) examination was used to observe the VMI status of both eyes before treatment. Vitreous macular adhesion (VMA), macular epiretinal membrane (MEM), and complete vitreous detachment (C-PVD) were defined as abnormalities in VMI. The VMA was classified as focal (≤1500 μm) and broad (＞1500 μm) depending on the diameter of the vitreous and macular adhesions on the OCT images. Before treatment, there were 12 eyes with abnormal VMI in study eyes, including 8 eyes with broad VMA, 3 eyes with focal VMA, and 1 eye with MEM; 12 eyes with abnormal VMI in control eyes: broad VMA in 7 eyes, focal VMA in 2 eyes, C-PVD in 2 eyes, and MEM in 1 eye. The average follow-up time after treatment was 16.4 months. During the follow-up period, OCT was performed monthly in a follow-up mode. Comparing the changes on VMI between before and after treatment in both eyes of patients, respectively. The chi-square test was used to compare the difference on VMI. Because the number of samples was ＜40, Fisher's exact test was used for the analysis.ResultsAt the final follow-up, 12 eyes with abnormal VMI in the study eyes, including 5 eyes with broad VMA, 2 eyes with focal VMA, 3 eyes with C-PVD, and 2 eyes with MEM. There were 6 eyes altered comparing with baseline. In the control eyes, there were 13 eyes with abnormal VMI, including 5 eyes with broad VMA, 7 eyes with C-PVD, and 1 eye with MEM. A total of 6 eyes changed on VMI comparing with baseline. At the final follow-up, there was no significant difference on VMI changes between the study eyes and its corresponding control eyes (P=0.053). In all eyes, a total of 4 eyes changed from focal VMA to C-PVD at the final follow-up, accounting for 80.0% of the total focal VMA; 3 eyes changed from broad VMA to C-PVD, accounting for 21.4% of the total broad VMA.ConclusionsRepeated anti-VEGF treatment has little effect on VMI. Regardless of anti-VEGF therapy, eyes with focal VMA appears to be more prone to C-PVD than the broad one.
Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs, including monoclonal antibodies (such as bevacizumab and ranibizumab) and fusion protein agents (such as aflibercept and conbercept) have been proven to be effective in the treatment of wet age-related macular degeneration (wAMD). However, there are still some patients with poor efficacy, such as no response to initial treatment or poor response, and even relapse during the course of treatment. In view of the different targets and molecular characteristics of anti-VEGF drugs, the switch of anti-VEGF drugs and the adjustment of delivery pattern, dosages and intervals have been the strategies to cope with the poor efficacy in clinic. However, there are some differences in the results of current studies. Overall, the recovery of retinal anatomical outcome achieves more benefits, and it is relatively difficult to improve visual acuity. To determine which regimen would get the biggest benefits, a large number of randomized controlled clinical trials and long study period will be needed.
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.