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.
ObjectiveTo observe the efficacy of intravitreal injection of conbercept (IVC) in the treatment of type 1 macular neovascularization (MNV) with different types of pigment epithelial detachment (PED) in neovascular age-related macular degeneration (nAMD). MethodsA retrospective clinical study. From June 2018 to June 2021, 42 patients with 42 eyes of nAMD type 1 MNV patients with different types of PED diagnosed in the ophthalmological examination of the Department of Ophthalmology, General Hospital of Central Theater Command were included in the study. All eyes underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT). The OCT examination was performed with a 3D-OCT 2000 instrument from Topcon Company in Japan. The fovea was scanned, and the PED height (PEDH), PED area (PEDA), PED volume (PEDV), and central foveal thickness (CFT) were measured. According to the OCT image features of PED, the affected eyes were divided into serous PED (sPED), fibrovascular PED (fPED), and hemorrhagic PED (hPED), and were grouped accordingly. Among the 42 eyes, 16 (38.1%, 16/42), 14 (33.3%, 14/42), and 12 (28.6%, 12/42) eyes were in the sPED group, fPED group, and hPED group, respectively. All patients received IVC treatment once a month for 3 consecutive months, and then on-demand treatment after assessment. BCVA and OCT were re-examined 3, 6, and 12 months after treatment, and the changes of BCVA, PEDH, PEDA, PEDV, and CFT in the affected eyes before and after treatment were compared, and repeated measures analysis of variance was used for statistical analysis. ResultsAt 12 months after treatment, the PEDH, PEDA and PEDV of the affected eyes in the sPED group, fPED group and hPED group were significantly lower than those before treatment, and the difference was statistically significant (P<0.05). The difference in the degree of improvement was －318.67±258.09 μm, －6.50±6.33 μm2, －1.95±1.78 μm3 in the hPED group; －119.31±224.13 μm, －0.86 ±5.00 μm2, －0.56±1.64 μm3 in the sPED group; fPED group were －53.93±92.51 μm, －0.76±2.54 μm2, －0.19±0.46 μm3. The improvement degree of the affected eyes in hPED group was significantly greater than that in sPED group and fPED group, and the difference was statistically significant (F=5.918, 6.029, 5.494; P＜0.05). Compared with the BCVA and CFT before treatment, 12 months after treatment, the difference was statistically significant in the fPED group and the hPED group (P＜0.05); there was no significant improvement in the sPED group (P＞0.05). There was no significant difference in the BCVA of the affected eyes in the three groups compared with those before treatment (F=0.817, 0.741, 0.848; P＞0.05). ConclusionConbercept can effectively improve or stabilize the visual function and anatomical morphology of eyes with type 1 MNV in nAMD with sPED, fPED and hPED, among which the anatomical effect is better for hPED.
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.
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.
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
ObjectiveTo observe the relationship between the response to anti-vascular endothelial growth factor (VEGF) drug treatment and single nucleotide polymorphism (SNP) genotype in patients with wet age-related macular degeneration (wAMD). MethodsA retrospective clinical study. From August 2019 to September 2020, 103 eyes of 103 wAMD patients diagnosed in Tianjin Medical University Eye Hospital were included in the study. Among them, there were 59 males (57.28%, 59/103) and 44 females (42.72%, 44/103); the average age was 68.74±7.74 years. The standard logarithmic visual acuity chart was used to detect the Best Corrected Visual Acuity of the affected eye and converted to the logarithmic minimum angle of resolution (logMAR) visual acuity during statistics. Optical coherence tomography was used to detect the central retinal thickness (CRT) of the affected eye. At the same time, the patient's high-density lipoprotein cholesterol (HDL-C) was tested. All eyes were treated with intravitreal injection of anti-VEGF drugs once a month for 3 months. Before the initial treatment, peripheral venous blood from the patient were collected. Interleukin-8 (IL-8), complement C3 gene (C3), complement factor H (CFH), liver lipase (LIPC), cholesterol ester transfer protein (CETP), ATP binding cassette subfamily a member 1 (ABCA1), lipoprotein lipase (LPL), fatty acid desaturation gene cluster (FADS1) SNP. According to gene frequency, genotypes are divided into wild type and mutant type were detected. Qualitative data such as the frequency difference of the genotype distribution in the clinical phenotype and the Hardy-Weinberg equilibrium of the genotype distribution were compared with the Chi-square test or Fisher's exact test. ResultsThere were fewer CRT responders in IL-8 rs4073 mutant (TA+AA) patients than wild-type (TT) [odds ratio (OR)=0.310, 95% confidence interval (CI) 0.106-0.910, P＜0.05). Among them, after the drug stratification test, the proportion of patients with IL-8 rs4073 locus TT genotype in the conbercept treatment group was less CRT non-responders (OR=0.179, 95% CI=0.034-0.960, P=0.033). Patients with LIPC rs2043085 mutant (CT+TT) with BCVA increased ≥0.2 logMAR are more likely than wild-type (CC) (OR=3.031, 95% CI 1.036-8.867, P＜0.05); HDL-C level was significantly lower Compared with wild type (CC), the difference was statistically significant (t=2.448, P=0.016). There was no significant difference in logMAR BCVA and CRT between IL-8 rs4073, LIPC rs2043085 mutant and wild-type patients before treatment (IL-8 rs4073: Z=－0.198, －1.651; P=0.843, 0.099; LIPC rs2043085: Z=－0.532, －0.152; P=0.595, 0.879). C3 rs 225066, CFH rs800292, CETP rs708272, ABCA1 rs1883025, FADS1 rs174547, LPL rs12678919 have no correlation with anti-VEGF drug treatment response. Conclusions Patients with wAMD are treated with anti-VEGF drugs. Those with IL-8 rs4073 locus A genotype may be less responsive to CRT. LIPC rs2043085 locus T genotypes may be relatively more responsive to BCVA.
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.
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.
Epigenetics has been very hot in the research of biomedicine. In addition to genetic factors, the occurrence of a disease is also influenced by environmental factors. Retinal vascular diseases are a type of irreversible blind eye disease, such as age-related macular degeneration and diabetic retinopathy. The retinal vessel changes are the major features of retinal vascular diseases, which are the result of interaction of multiple environmental factors and genes. Epigenetic modification mainly includes DNA methylation, histone modification, and non-coding RNA regulation. Epigenetic mechanisms mediate the effects of environmental factors on genes related to retinal vascular diseases, and affect the eventual development of the diseases. Therefore, ophthalmologists should keep eyes close on the role of epigenetics in retinal vascular diseases, track the progress of epigenetic methods in the treatment of retinal vascular diseases, and pay attention to the application prospects of epigenetics. Finding the epigenetic regulators of these diseases can not only deepen the understanding of the pathological mechanism of these diseases, but also provide new ideas for the diagnosis and treatment of these diseases.