Choroidal neovascularization is the leading causes of central vision loss in wet age-related macular degeneration (wAMD) patients. Smoking not only aggravates the incidence and severity of the choroidal neovascularization of wAMD, but also affects the clinical treatment, making the prognosis worse. Nicotine, as an important harmful substance in tobacco, is an easily addictive and highly toxic alkaloid. Animal experiments and clinical studies have confirmed that nicotine can aggravate wAMD by mediating angiogenesis through nicotinic acetylcholine receptor, bone marrow blasts, inflammation, complement system, etc. Therefore, in order to early take appropriate intervention measures to prevent and delay the development, we should actively explore the exact pathogenesis by which nicotine aggravates the choroidal neovascularization.
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 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 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.
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.
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.
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.
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.
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.
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.