【Abstract】Objective To evaluate the status of vascular endothelial growth factor (VEGF) expression in breast carcinoma and benign disease and define the relationship with age,menopause, tumor size，clinical stage，distant metastasis and lymph node metastasis. Methods Seventy cases of invasive ductal breast carcinomas,30 benign breast diseases and 7 adjacent nonneoplastic specimens were assessed for VEGF protein expression by immunohistochemistry LSAB method. Results VEGF were expressed more frequently in breast cancer than in benign diseases.VEGF was significantly correlated with axillary lymph node metastasis and distant metastasis,whereas no statistical correlation with other factors. Conclusion VEGF status has certain value to make differential diagnosis between malignant and benign breast diseases and predict the possibilities of distant and lymph node metastasis.
ObjectiveTo observe the effect of intravitreal injection of conbercept in the treatment of retinopathy of premature (ROP) and to analyze the factors related to the therapy.MethodsA retrospective study. A total of 57 patients (57 eyes) with pre-threshold type 1 (30 patients, 30 eyes), threshold ROP (21 patients, 21 eyes) and acute aggressive posterior ROP (APROP, 6 patients, 6 eyes)) from premature infants by retinal screening in Henan Provincial People’s Hospital during October 2017 and June 2018 were enrolled in this study. All children were received routinely intravitreal injected 10 mg/ml conbercept 0.025 ml (0.25 mg) within 24 hours after diagnosis. Fundus examination was performed 7 days after injection. The interval of examination was 1−3 weeks according to fundus conditions. The mean follow-up was 30.1±4.6 weeks. For patients with relapse or no response to treatment, repeated intravitreal injection of conbercept or laser photocoagulation therapy was given. The retinal blood vessels of the affected eyes were observed. Logistic stepwise regression analysis was used for the correlation test of multiple factors.ResultsAmong 57 eyes, 49 eyes and 8 eyes were treated with 1 or 2 times of intravitreal injection of conbercept. After 24 weeks of treatment, in 57 eyes, 26 eyes were cured (45.6%), 22 eyes improved (38.6%), 8 eyes relapsed (14.0%), and 1 eye aggravated (1.8%). The recurrence time was 12.9±4.5 weeks after the first injection, and the corrected gestational age was 49.0±6.7 weeks. There were significant differences in initial injection time, lesion range among the cure, improved and recurrence eyes (F=5.124, 7.122; P＜0.01, ＜0.01). Parameters of ROP condition, including ROP diagnosis (pre-threshold type 1, threshold and APROP), zone (zone 1 and 2), stage (stage 2 and 3) and plus lesions, were significant different among the cure, improved and recurrence eyes (χ2=11.784, 14.100, 6.896, 9.935; P＜0.01, ＜0.01, ＜0.05, ＜0.01). Logistic stepwise regression analysis showed that the recurrence rate was correlated with ROP zone, more likely recurrence at zone 1 than zone 2 (Wald=9.879, OR=27.333, P=0.002). No injection-related complications such as endophthalmitis, cataract and glaucoma were found during treatment and follow-up period.ConclusionsIntravitreal injection of conbercept is effective in the treatment of ROP without obvious adverse reactions. Lesion zoning is associated with recurrence after treatment.
ObjectiveTo observe the correlation analysis between the deep-superficial flow-density ratio (DSFR) and treatment response of macular edema secondary to branch retinal vein occlusion (BRVO).MethodsForty-eight patients（48 eyes）with macular edema secondary to BRVO from December 2018 to December 2019 in the Department of Ophthalmology of Beijing Hospital were enrolled in this study. There were 29 males (29 eyes) and 19 females (19 eyes), with the mean age of 58.77±10.88 years. All eyes were treated with intravitreal injection of ranibizuma once a month for 3 months, and then treated as needed. According to the central retinal thickness (CRT) 12 months after treatment, the patients were divided into good response group (CRT≤250 μm) and refractory group (CRT＞250 μm). The flow density in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) of all subjects was measured by optical coherence tomography angiography. The flow density of DCP and SCP measured at 3 follow-up times was selected and DSFR was calculated. The DSFR was recorded by the Study for the Treatment of Diabetic Retinopathy (ETDRS) -grid and Nine-grid. The flow density of DCP, SCP and DSFR were compared between the two groups by paired t test. At 3 months post-treatment, the efficacy of DSFR in ME treatment response was evaluated according to area under curve (AUC) of receiver operating characteristic. Univariate and multivariate binary logistic regression were used to analyze the factors affecting the response to ME treatment.ResultsAt 12 months after treatment, there were 27 eyes in good response group and 21 eyes in refractory group. There was no statistical significance in the flow density of DCP (t=1.804, 1.064, 0.660) and SCP (t=0.581, 0.641, 0.167) and DSFR (t=0.393、－0.553、0.474) in all area of response group and refractory group using ETDRS-GRID recording method (P＞0.05). The SCP, DCP and DSFR of the most severe non-perfusion area were (27.10±5.70) %, (28.33±8.95) %, 1.35±0.54 and (27.54±6.70) %, (29.11±0.42) %, 1.01±0.40 in the response group and refractory group, respectively. There was no significant difference in the flow density of DCP and SCP between the two groups (t=－0.237, －0.340; P＞0.05). The difference of DSFR between two groups was statistically significant (t=2.288, P=0.024). Univariate and multivariate binary logistic regression analysis showed that DSFR in the most severe non-perfusion area was associated with ME response (odds ratio=0.212, 0.085; P=0.027, 0.024). The AUC was used to evaluate the efficacy of DSFR in ME treatment response, the results showed that the AUC was 0.800, P=0.001, Youden index was 1.348, sensitivity was 67.7%, and specificity was 86.7%.ConclusionsDSFR reduction is more common in BRVO secondary to ME patients. DSFR correlates with ME treatment response.
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.
Objective To summarize the role of matrix metalloproteinases (MMPs) in occurrence and development of gastric cancer. Methods Domestic and international publications online involving MMPs of gastric cancer in recent years were collected and reviewed. Results The occurrence and development of gastric cancer was a multi-step and multi-factorial complicated progress, whose etiology and pathogenesis were still unclarified. MMPs were a class of proteolytic enzymes, which played an important role in the proliferation, metastasis, angiogenesis of gastric cancer and apoptosis of tumor cells and their surrounding normal cells by regulating the microenvironment of the growth of tumor. Conclusion MMPs promote the evolution of gastric cancer in variable ways, the mechanisms of which should be comprehended to provide a theoretical basis for the future treatment of gastric cancer.
Objective Tissue engineered bone implanted with sensory nerve can effectively promote angiogenesis and repair of bone defects. To investigate the effects of calcitonin gene-related peptide (CGRP) on proliferation and migration of human umbilical vein endothelial cells (HUVECs) for further revealing the mechanism of tissue engineered bone implanted with sensory nerve promoting angiogenesis. Methods HUVECs were collected from human umbilical core, and identified through von Willebrand factor (vWF) and CD31 immunofluorescence. The HUVECs were treated with CGRP and were ivided into 6 groups according to CGRP concentration: group A (0 mol/L), group B (1 × 10—12 mol/L), group C (1 × 10—11 mol/L), group D (1 × 10—10 mol/L), group E (1 × 10—9 mol/L), and group F (1 × 10—8 mol/L). The expression of the CGRP1 receptor (CGRP1R) was observed in HUVECs by cell immunofluorescence. The growth rate of HUVECs was detected through AlarmarBlue at 1, 2, 3, 4, and 5 days. Transwell chamber was used to detect the abil ity of cell migration. ELISA assay was used to detect the vascular endothel ial growth factor (VEGF) secretion and the protein expression of focal adhesion kinase (FAK) was examined using Western blot. Results HUVECs were identified through morphology, vWF and CD31 immunofluorescence. HUVECs expressed CGRP1R. CGRP could stimulate HUVECs prol iferation in a time- and concentration-dependent manners; the cell growth rates of groups B-F were significantly higher than that of group A at all time (P lt; 0.05); group F had highest cell growth rate. The number of cell migration of group B-F was significantly higher than that of group A (P lt; 0.05), which increased more than 3 times. Groups B-F had higher amount of VEGF than group A (P lt; 0.05), and groups C and D had highest amount of VEGF. FAK expression of groups B-F was significantly increased at 3, 7, and 10 days after CGRP treatment when compared with group A (P lt; 0.05). Conclusion CGRP may enhance the proliferation and migration of HUVECs by increasing the secretion of VEGF and expression of FAK.
Diabetic retinopathy (DR) is a common ocular complication in diabetic patients, which is chronic and progressive and seriously impairs visual acuity. The rapid occurrence and progress of cataract in diabetic patients is also one of the important reasons for visual impairment in DR patients. Compared with non-diabetic patients, diabetic patients have higher risk of complications after cataract surgery. Studies have shown that anti-vascular endothelial growth factor (VEGF) therapy after cataract surgery can prevent the aggravation of diabetic macular edema in DR patients. However, due to the lack of systematic review of the clinical effect of anti-VEGF drugs in DR patients undergoing cataract surgery, the use of anti-VEGF drugs is relatively conservative in clinic. It is believed that with the deepening of research and the progress of clinical trials, the wide application of anti-VEGF drugs in clinical practice is expected to provide more accurate and effective treatment for DR patients in the future.
Objective To investigate the factors associated with short-term elevation of intraocular pressure after ranibizumab intravitreal injection. Methods 292 eyes of 292 patients who were diagnosed retinopathy and suitable to receive ranibizumab intravitreal injection were enrolled in this prospective clinical study. There were 157 males and 135 females. 193 patients diagnosed with age-related macular degeneration and 99 other retinopathy patients. Mean age of patients was 62.75±13.74 years. All subjects underwent systemic and comprehensive ophthalmology examinations. The mean BCVA was 0.68±0.47 logMAR. Mean basal intraocular pressure was 18.1 mmHg (1 mmHg=0.133 kPa). All patients received intravitreal injection with 0.05 ml of ranibizumab (0.5 mg). The intraocular pressure were measured by non-contact tonometer at 10, 30, 120 minutes and 1 day after injection in a sitting position. The patients were grouped by the changes of intraocular pressure 10 minutes after injection. The elevation was more than 10 mmHg as elevation group and less than 10 mmHg as stable group. Analyze the possible related factors with elevation of intraocular pressure after ranibizumab intravitreal injection by comparing the different datum of two groups. Results The mean intraocular pressure were 23.8, 20.5, 19.9 and 17.4 mmHg at 10, 30, 120 minutes and 1 day after injection. The significant elevation level were 5.8, 2.4, 1.8, −0.7 mmHg compared with basal intraocular pressure. Among 292 eyes, intraocular pressure elevation in 68 eyes and stabled in 224 eyes. The age (Z=−0.732), gender (χ2=1.929), right or left eye (χ2=2.910), BCVA (Z=−0.039), diseases (χ2=2.088) were no significant difference between two groups (P＞0.05). The injection number (Z=−2.413, P=0.001), basal intraocular pressure (Z=−3.405, P=0.016) and elevations after injection (Z=−11.501, −8.366, −5.135, −3.568; P＜0.01) were significantly different comparing two groups (P＜0.05). By logistic regression analysis, basal intraocular pressure was positively correlated with the elevation of intraocular pressure 10 minutes after injection (B=−0.844, OR=0.43, 95%CI 0.24−0.76, P=0.004). Patients with higher basal intraocular pressure may occur intraocular pressure elevation after ranibizumab intravitreal injection much probably. Conclusions The factors associated with short-term elevation of intraocular pressure after ranibizumab intravitreal injection were basal intraocular pressure. The higher basal intraocular pressure, the higher risk to gain elevation of intraocular pressure after injection.
ObjectiveTo investigate the efficacy and safety of traditional laser photocoagulation, laser combined with intravitreal injection of anti-vascular endothelial factor (anti-VEGF) drugs and intravitreal injection of anti-VEGF drugs alone in Coats disease. MethodsThe patients diagnosed as Coats disease stage 2B-3A2 in Department of Ophthalmology, Eye and ENT Hospital of Shanghai Medical College of Fudan University from December 2016 to November 2019 were included in this study. Patients were divided into three groups, including laser group, combined group and drug group, according to the different treatment. In the laser group, the initial treatment was traditional laser photocoagulation alone. In the drug group, the anti-VEGF drug was injected into vitreous once a month for three months. The initial treatment of the eyes in the combined group was laser combined with intravitreal injection of anti-VEGF drugs, or laser treatment within 1 week after anti-VEGF drug treatment. The follow-up time was more than 6 months, and best-corrected visual acuity (BCVA), ultra-wide-angle fundus photography, and fluorescein fundus angiography were performed during follow-up. The treatment efficiency, subretinal fluid (SRF), macular edema, BCVA and complications were compared among the three groups. ResultsAmong 60 patients (60 eyes), there were 55 males (55 eyes) and 5 females (5 eyes), with the mean age of 17.1±2.0 years. Among 60 eyes, there were 26 eyes in 2B stage, 23 eyes in 3A1 stage, and 11 eyes in 3A2 stage. Twenty patients (20 eyes) was in the laser group, combined group and drug group, respectively. After the initial treatment of all eyes in the drug group, the abnormal blood vessels did not regress significantly; the absorption and increase of SRF were 4 (20.0%, 4/20) and 5 (25.0%, 5/20) eyes, respectively. Supplementary laser therapy was given to 16 eyes, and vitrectomy (PPV) was given to 4 eyes. Among the 16 eyes treated by laser, 10 eyes were effective (50.0%, 10/20); vitreous hemorrhage, fibrous membrane hyperplasia, and complicated cataract occurred in 1, 1, and 2 eyes during the treatment, respectively, and PPV was given again in all eyes. Recurrent and persistent macular edema occurred in 4 and 1 eyes, respectively. Among the eyes in the combined group, treatment were effective in 11 eyes (55.0%, 11/20); 5, 2, and 2 eyes had SRF, fibrous membrane hyperplasia, and complicated cataract during the treatment, and PPV was given again; the edema was repeated and persisted in 1 eye, respectively. Among the affected eyes in the laser group, 15 eyes (75.0%, 15/20) were treated effectively; 2, 2, and 1 eyes developed a large number of vitreous hemorrhage, fibrous membrane hyperplasia, and complicated cataract during the treatment, and PPV was given again. ConclusionsAnti-VEGF drugs alone are ineffective in the treatment of Coats disease, and ablation of other abnormal blood vessels is needed. In the treatment of Coats disease, anti-VEGF drugs can not only promote the absorption of SRF, but also may lead to its increase, and the application should be cautious.
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.