Objective To investigate the role of vascular endothelial growth factor ( VEGF) in the pathogenesis of emphysema and its relationship with tumor necrosis factor alpha ( TNF-α) . Methods 48 rats were randomly divided into four groups, ie. a normal control group, an emphysema group, a rhTNFR∶Fc intervention group, and a sham intervention group. The rats in the emphysema group, the rhTNFR: Fc intervention group, and the shamintervention group were exposed to cigarette smoking for 80 days. After 30 days of exposure, rhTNFR: Fc hypodermic injection was administered in the rhTNFR: Fc intervention group while placebo was injected in the sham intervention group as control. Lung tissue sections were stained by hematoxylin and eosin. Mean linear intercept ( MLI) and mean alveolar numbers ( MAN) were measured to estimate the extent of emphysema. The level of TNF-αin serumand BALF, and the level of VEGF in BALF were measured with ELISA. Results In the emphysema group, MLI was higher and MAN was lower than those in the normal control group. Moreover, the levels of TNF-αin serum and BALF were higher, and thelevel of VEGF in BALF was lower significantly ( P lt;0. 05) . After the intervention with rhTNFR∶Fc, MAN increased and the serum TNF-αdecreased significantly compared with the emphysema group ( P lt; 0. 05) .However there were no significant differences in MLI, VEGF, and TNF-α in BALF ( P gt; 0. 05 ) . No correlation was found between the level of TNF-αand VEGF in BALF in the emphysema group. Conclusion VEGF and TNF-αare related to the pathogenesis of emphysema of smoking rats, and may contribute to the development of emphysema in different pathways.
Objective To investigate the inhibitory effects of IBI302 on experimental choroidal neovascularization (CNV). Methods Affinity of IBI302 to vascular endothelial growth factor (VEGF) family cytokines (including VEGF-A165, VEGF-A121 and placental growth factor PlGF) and complements (C3b, C4b) was determined by enzyme-linked immunosorbent assay (ELISA). The antagonist effect of IBI302 on VEGF was measured by proliferation, migration and tube formation tests of human umbilical vein endothelial cells (HUVEC). The anti-complement activity of IBI302 was measured by hemolysis test mediated by complement classical pathway and alternative pathway. Rhesus laser-induced CNV model was divided into 5 groups including model control group, bevacizumab group, IBI302 0.25 mg group, IBI302 0.50 mg group and IBI302 1.25 mg group. Fluorescein angiography and optical coherence tomography were performed on these monkeys at 14 and 28 days after drug delivery to observe the fluorescein leakage area and retinal thickness. The aqueous VEGF concentration was measured at 29 days after drug delivery. Results IBI302 showed good affinity to VEGF-A165, VEGF-A121 and PlGF, as well as C3b and C4b. IBI302 significantly inhibited the proliferation, migration and tube formation of HUVEC induced by VEGF-A165. IBI302 inhibited the hemolysis induced by complements obviously. At 14 and 28 days after drug delivery, the area of fluorescein leakage and retinal thickness in IBI302 0.25 mg group, IBI302 0.50 mg group, IBI302 1.25 mg group were reduced. The differences of the area of fluorescein leakage and retinal thickness in three IBI302 groups were not significant (P > 0.05). At 29 days after drug delivery, the VEGF concentration in the aqueous of rhesus monkey in bevacizumab group [(38.644±6.521) pg/ml] was decreased than that in model control group [(94.203±17.360) pg/ml], the difference was significant (P < 0.05). The VEGF concentration in the aqueous of rhesus monkey in three IBI302 groups were less than 31.300 pg/ml. Conclusion IBI302 inhibited experimental CNV through blocking the activity of VEGF and complement.
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.
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.
ObjectiveTo observe the efficacy of conbercept in the treatment of different types of diabetic macular edema (DME).MethodsA retrospective clinical study. From March 2019 to March 2021, 136 eyes of 136 patients with DME diagnosed in Department of Ophthalmology of Xi'an No.3 Hospital were included in the study. Among them, there were 65 males and 71 females; the average age was 56.65±8.65 years. All patients underwent best corrected visual acuity (BCVA), optical coherence tomography (OCT) examination, and glycosylated hemoglobin level (HbA1c) examination. Early Treatment Diabetic Retinopathy Study visual acuity chart was used for BCVA examination, which was converted into the logarithmic minimum angle of resolution (logMAR) visual acuity during statistics. An OCT instrument was used to measure the central retinal thickness (CRT) of the macula. According to the characteristics of OCT, DME was divided into diffuse retinal thickening (DRT) type, cystoid macular edema (CME) type, serous retinal detachment (SRD) type, mixed type, and grouped accordingly, respectively, about 30, 38, 33, 35 eyes. There was no significant difference in age (F=1.189), sex ratio (χ2=1.331), and HbA1c level (F=3.164) of the four groups of patients (P＞0.05). All eyes were treated with intravitreal injection of 10 mg/ml conbercept 0.05 ml (including conbercept 0.5 mg) once a month for 3 consecutive times, and then treated as needed after evaluation. BCVA and OCT examinations were performed 1, 3, and 6 months after treatment with the same equipment and methods as before treatment. The changes of BCVA and CRT before and after treatment were compared and observed. For measurement data subject to normal distribution, one-way analysis of variance was performed for comparison between groups; χ2 test was performed for comparison of count data.ResultsBefore treatment, the logMAR BCVA of the eyes in the DRT group, CME group, SRD group, and mixed group were 0.68±0.11, 0.69±0.15, 0.71±0.12, 0.73±0.14, and CRT was 631.4±50.7, 640.6±55.7, 652.3±63.4, 660.4±61.8 μm. Compared with before treatment, 1, 3, 6 months after treatment, DRT group (BCVA: t=8.139, 11.552, 11.672; CRT: t=16.163, 21.653, 25.855), CME group (BCVA: t=8.923, 9.995, 13.842; CRT: t=16.163, 21.653, 25.855), SRD type group (BCVA: t=5.171, 7.315, 6.051; CRT: t=9.099, 13.731, 21.306), mixed type group (BCVA: t=5.072, 6.939, 7.142; CRT: t=6.920, 15.352, 17.538) The BCVA of the affected eyes was significantly increased, and the CRT was significantly decreased, and the difference was statistically significant (P＜0.05). At 6 months after treatment, the differences in logMAR BCVA and CRT of the 4 groups of eyes were statistically significant (χ2=58.478, 64.228; P＜0.05). The average number of injections in the eyes of the DRT group, CME group, SRD group, and mixed group were 3.37±1.35, 3.68±1.38, 4.18±1.40, 4.13±1.50 times, respectively. Compared with the average number of injections in the eye, the difference was statistically significant (χ2=9.139, P=0.028).ConclusionsConbercept can effectively reduce CRT and increase BCVA in eyes with different types of DME. Compared with SRD type and mixed type, DRT and CME type eye are more effective in improving vision, CRT reduction degree is greater, and the number of injections is less.