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.
Wet age-related macular degeneration (wAMD) is caused by choroidal neovascularization (CNV), which occurs when the choroidal new capillaries reach the RPE layer and photoreceptor cell layer through the ruptured Bruch membrane, leading to neovascularization bleeding, leakage, and scarring. In view of the important role of VEGF in the development of CNV, targeted therapy with various intraocular anti-VEGF drugs is the first-line treatment for wAMD. However, the efficacy of anti-VEGF drugs in the treatment of wAMD is affected by a variety of factors, and some patients still have problems such as unresponsiveness, drug resistence, tachyphylaxis, long-term repeated injections, and severe adverse effects. It is the direction of future researches to deeply explore the physiological and pathological process of wAMD, find the cause of CNV formation, and seek better therapies.
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.
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 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.
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.
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.
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
With the rapid development of fundus imaging technology, it is of great significance to establish a new naming system for neovascular age-related macular degeneration (nAMD) based on the multi-mode imaging. In 2020, an international panel of retina specialists, imaging and image reading center experts, and ocular pathologists reached a consensus after repeated discussions, a new name for nAMD subtype and related lesions was established based on the previous knowledge of fundus fluorescein angiography and pathology, combining indocyanine green angiography, optical coherence tomography and optical coherence tomography angiography with current pathological knowledge, in order to help ophthalmologists to study nAMD. The consensus proposed the term "macular neovascularization" and classified it into type 1, type 2 and type 3. Many lesions related to macular neovascularization, such as pigment epithelial detachment, hemorrhage, fibrosis, rip of retinal pigment epithelium and so on, were named. The new designation will help improve clinical communication between different studies, establish standard definitions and terms between reading centers and researchers, and further promote the understanding and communication of nAMD among ophthalmologists.
ObjectiveTo observe the short-term effects of intravitreal injection of aflibercept (IVA) for initial treatment and dressing change on exudative age-related macular degeneration (eAMD). MethodsA retrospective clinical study. From June 2018 to February 2021, forty-nine eAMD eyes of 38 patients who underwent IVA treatment in Department of Ophthalmology of Central Theater Command Hospital of People’s Liberation Army were included in the study. Among them, there were 24 males with 29 eyes and 14 females with 20 eyes; the average age was 66.82±8.71 years. All affected eyes were treated with IVA. The initial loading dose was 2.0 mg, which was injected once a month for 3 consecutive months, followed by monthly review and treatment as needed. Of the 49 eyes, 26 eyes were initially treated (initial treatment group), they were diagnosed within 3 months of the first onset and followed by IVA treatment, and no intraocular drugs and surgery were performed from the onset to the first diagnosis. Twenty-three eyes were treated with drug exchange therapy (dressing change group), they received intravitreal injection of ranibizumab and/or conbercept more than 4 times 6 months before the replacement therapy, during which there was persistent interlaminar cystoid edema and/or subretinal fluid (SRF) in the macular area and no improvement in pigment epithelial detachment (PED). Before IVA treatment, there were no statistically significant differences in the best corrected visual acuity (BCVA), foveal thickness (CMT), PED height (PEDH), and PED volume (PEDV) of the two groups of eyes before IVA treatment (P＞0.05). The same equipment and methods as before treatment were used for related examinations, and the changes of BCVA, CMT, PEDH, PEDV and complications of the two groups of eyes were recorded in 1, 3, and 6 months after treatment. The comparison of BCVA, CMT, PEDH, and PEDV between the two groups were used repeated measures analysis of variance. ResultsSix months after treatment, the number of IVA injections in the eyes of the initial treatment group and dressing change group were 4.15±0.73 and 4.39±0.72 times, respectively, and the difference was not statistically significant (t=?1.141, P=0.260). The BCVA, CMT, PEDH, and PEDV of the the initial treatment group (F=5.345, 22.995, 6.764, 5.425) and the dressing change group (F=12.519, 15.576, 8.843, 9.406) were significantly improved compared before treatment with 1, 3, and 6 months. All were statistically significant (P＜0.05). There was no significant difference in BCVA, CMT, PEDH, and PEDV between the initial treatment group and the dressing group at each time point after treatment (F=1.741, 0.069, 0.876, 3.455; P＞0.05). During the follow-up period, none of the affected eyes had complications such as persistent intraocular pressure increase, endophthalmitis, and retinal pigment epithelial tear. ConclusionsIVA can improve eyesight of patients with eAMD and reduce CMT, PEDH, and PEDV. The initial treatment and dressing change have the same effect.
