Anti-vascular endothelial growth factor drugs combined with laser photocoagulation maintain retinal ganglion cell integrity in patients with diabetic macular edema: study protocol for a prospective, non-randomized, controlled clinical trial

The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells,affecting vision.The major clinical treatments for diabetic macular edema are anti-vascular endothelial growth factor drugs and laser photocoagulation.However,although the macular thickness can be normalized with each of these two therapies used alone,the vision does not improve in many patients.This might result from the incomplete recovery of retinal ganglion cell injury.Therefore,a prospective,non-randomized,controlled clinical trial was designed to investigate the effect of anti-vascular endothelial growth factor drugs combined with laser photocoagulation on the integrity of retinal ganglion cells in patients with diabetic macular edema and its relationship with vision recovery.In this trial,150 patients with diabetic macular edema will be equally divided into three groups according to therapeutic methods,followed by treatment with anti-vascular endothelial growth factor drugs,laser photocoagulation therapy,and their combination.All patients will be followed up for 12 months.The primary outcome measure is retinal ganglion cell-inner plexiform layer thickness at 12 months after treatment.The secondary outcome measures include retinal ganglion cell-inner plexiform layer thickness before and 1,3,6,and 9 months after treatment,retinal nerve fiber layer thickness,best-corrected visual acuity,macular area thickness,and choroidal thickness before and 1,3,6,9,and 12 months after treatment.Safety measure is the incidence of adverse events at 1,3,6,9,and 12 months after treatment.The study protocol hopes to validate the better efficacy and safety of the combined treatment in patients with diabetic macula compared with the other two monotherapies alone during the 12-month follow-up period.The trial is designed to focus on clarifying the time-effect relationship between imaging measures related to the integrity of retinal ganglion cells and best-corrected visual acuity.The trial protocol was approved by the Medical Ethics Committee of the Affiliated Hospital of Beihua University with approval No.(2023)(26)on April 25,2023,and was registered with the Chinese Clinical Trial Registry(registration number:ChiCTR2300072478,June 14,2023,protocol version:2.0).

Nomogram for predicting short-term response to anti-vascular endothelial growth factor treatment in neovascular age-related macular degeneration:An observational study

BACKGROUND Anti-vascular endothelial growth factor(anti-VEGF)therapy is critical for managing neovascular age-related macular degeneration(nAMD),but understanding factors influencing treatment efficacy is essential for optimizing patient outcomes.AIM To identify the risk factors affecting anti-VEGF treatment efficacy in nAMD and develop a predictive model for short-term response.METHODS In this study,65 eyes of exudative AMD patients after anti-VEGF treatment for≥1 mo were observed using optical coherence tomography angiography.Patients were classified into non-responders(n=22)and responders(n=43).Logistic regression was used to determine independent risk factors for treatment response.A predictive model was created using the Akaike Information Criterion,and its performance was assessed with the area under the receiver operating characteristic curve,calibration curves,and decision curve analysis(DCA)with 500 bootstrap re-samples.RESULTS Multivariable logistic regression analysis identified the number of junction voxels[odds ratio=0.997,95%confidence interval(CI):0.993-0.999,P=0.010]as an independent predictor of positive anti-VEGF treatment outcomes.The predictive model incorporating the fractal dimension,number of junction voxels,and longest shortest path,achieved an area under the curve of 0.753(95%CI:0.622-0.873).Calibration curves confirmed a high agreement between predicted and actual outcomes,and DCA validated the model's clinical utility.CONCLUSION The predictive model effectively forecasts 1-mo therapeutic outcomes for nAMD patients undergoing anti-VEGF therapy,enhancing personalized treatment planning.

Efficacy and safety of anti-vascular endothelial growth factor agents on corneal neovascularization: A meta-analysis

BACKGROUND Corneal neovascularization(CoNV)is the second major cause of blindness.Vascular endothelial growth factor(VEGF)inhibitors,e.g.,bevacizumab,have been used to prevent CoNV.AIM We conducted an updated systematic review and meta-analysis of clinical trials to examine the efficacy and safety of anti-VEGF in CoNV.METHODS A literature search was conducted using three electronic databases.Mean difference(MD),standard mean difference(SMD),and relative risk(RR)are used to estimate the effect size.RESULTS Nine randomized controlled and three non-randomized trials were obtained.The pooled results demonstrated a significant reduction of CoNV area/Length(SMD=-1.17,95%CI:-1.58 to-0.75),best corrected visual acuity(MD=-0.54,95%CI:-0.91 to-0.17),and graft rejection(RR=0.44,95%CI:0.24 to 0.8)and failure(RR=0.39,95%CI:0.19 to 0.78)rates in the anti-VEGF group than the placebo group.A non-significant reduction of the epithelial defect was also observed in the bevacizumab group compared with the placebo(RR=0.56,95%CI:0.30 to 1.06).Compared with a placebo,the unsynthesizable trials also support that bevacizumab improves visual acuity,CoNV,graft rejection,and failure rates.Trials reporting other comparisons revealed the superiority of combined remedy with bevacizumab compared to other treatments in reducing CoNV.CONCLUSION Anti-VEGF agents,mainly bevacizumab,are an effective and safe treatment for CoNV of all causes and prevent corneal graft rejection and failure in corneal transplantation.

Efficacy of internal limiting membrane peeling for diabetic macular edema after preoperative anti-vascular endothelial growth factor injection

AIM:To explore the efficacy of minimally invasive vitrectomy(MIV)with or without internal limiting membrane(ILM)peeling on the treatment of diabetic macular edema(DME)in proliferative diabetic retinopathy(PDR)combining with preoperative anti-vascular endothelial growth factor(anti-VEGF)injection.METHODS:Totally 132 eyes(132 patients)diagnosed PDR with DME were included between June 2015 and June 2018 in Tianjin Eye Hospital.The single MIV treatment group included 68 eyes and the MIV combined with ILM peeling group included 64 eyes.Anti-VEGF drugs were injected intravitreally 1wk before the operation and the period of follow-up was 1 to 3y.Best-corrected visual acuity(BCVA),central retinal thickness(CRT),total macular volume(TMV),macular edema(ME)severity,intraocular pressure(IOP),and complications were recorded.Prognostic factors of visual acuity following ILM peeling were analyzed.RESULTS:The BCVA was higher than preoperative values at 1,3,6,and 12mo after surgery in both groups(all P<0.05).At 6 and 12mo,the BCVA of the combined group was significantly higher than that of the MIV only group(0.52±0.23 v/s 0.64±0.29 IogMAR,P=0.011 in 6mo;0.41±0.25\/s 0.52±0.25 IogMAR,P=0.008 in 12mo).Mean CRT values postoperative were significantly lower than preoperative values in both groups from the 1^(st) month(lmo 397.65±106.18 vs 451.94±118.88 μm in MIV only group;388.88±108.68 v/s 464.36±111.53 μm in combined group;both P<0.05)and decreased gradually.The differences between the two groups were statistically significant at 3,6,and 12mo(P=0.004,0.003,0.00 respectively).The TMV was decreased from the 3^(rd) month in the single treatment group(3mo 11.14±1.66 vs 12.20±2.09 mm^(3),P<0.05).At 12mo,the proportion of eyes with edema that had CRT more than 350μm was significantly lower than before surgery(13.24%vs 77.94%in MIV only group;1.56%vs 81.25%in combined group;both P<0.05).There was no significant difference in the recurrence incidence of macular epiretinal membrane,ME,transient IOP increase,vitreous rebleeding,or traction retinal detachment between the two groups.BCVA after ILM excision was positively correlated with the CRT and ME degree before and after surgery(r=0.430,0.485,respectively;P<0.05).CONCLUSION:MIV combined with ILM peeling accelerates the absorption of ME,improves vision,reduces the postoperative CRT and TMV,and reduces the recurrence rate of postoperative ME.

Macular hole closure following anti-vascular endothelial growth factor injection in an eye with myopic choroidal neovascularization

Dear Editor,I am Cheolmin Yun,from the Department of Ophthalmology,Korea University College of Medicine.I write to present a case report of a female patient with a myopic patient suffering from atrophic choroidal neovascularization（CNV）and a full thickness macular hole（FTMH）,who was treated with an intravitreal anti-vascular endothelial growth factor （VEGF） injection without vitrectomy.

Real-world outcomes of anti-vascular endothelial growth factor therapy for retinal vascular vein occlusion in Tibet,China

AIM: To evaluate the outcomes of intravitreal antivascular endothelial growth factor(anti-VEGF) agents for patients with retinal vein occlusion(RVO) related-macular edema(ME) in Tibetan.METHODS: A retrospective, observational, single-center study. The demographic and clinical data of 90 RVO Tibetan patients(93 eyes) treated with either ranibizumab or conbercept in Tibet Autonomous Region People’s Hospital from Jan 2018 to December 2019 were collected.RESULTS: The mean patient age was 56.8±10.6y, 45(50%) of them were female. The mean living altitude was 3867.8±567.9 m. At the last visit, the best-corrected visual acuity(BCVA) significantly increased(52.2±21.8 letters) in comparison with the baseline(38.2±24.1 letters, P<0.001);while the central retinal thickness(CRT) significantly reduced(245.5±147.6 μm) in comparison with the baseline(504.1±165.2 μm, P<0.001). The 43.0% of the eyes gained≥15 letters, 60.2% of the eyes gained ≥10 letters, and 78.5% of the eyes gained ≥5 letters. No vision loss was noted in 92.5% of the eyes, 4 eyes lost more than 10 letters during follow-up period. The mean number of injections was 2.4±1.8. No severe ocular or systemic adverse events related to either the drug or injection were noted.CONCLUSION: Anti-VEGF therapy is effective and safe in Tibetan patients for the treatment of RVO related ME.

Efficacy and mechanism of anti-vascular endothelial growth factor drugs for diabetic macular edema patients

BACKGROUND Diabetes is a serious public health concern in China,with 30%of patients developing retinopathy,and diabetic macular edema(DME)having the biggest impact on vision.High blood glucose level can cause retinal cell hypoxia,thus promoting vascular endothelial growth factor(VEGF)formation and increasing vascular permeability,which induces DME.Moreover,cell hypoxia can accelerate the rate of apoptosis,which leads to the aging of patients.In severe cases,optic cell apoptosis or retinal fibrosis and permanent blindness may occur.AIM To investigate and compare the efficacy,mechanism,and differences between two anti-VEGF drugs(Compaq and ranibizumab)in DME patients.METHODS Ninety-six patients with DME who attended our hospital from April 2018 to February 2020 were included and randomly divided into two groups(Compaq group and ranibizumab group).The groups received vitreal cavity injections of 0.5 mg Compaq and 0.5 mg ranibizumab,respectively,once a month.The best corrected visual acuity(BCVA),intraocular pressure(IOP),macular retinal thickness(CMT),macular choroidal thickness(SFCT),foveal no perfusion area(FAZ),superficial capillary density,deep capillary density,treatment effect,and adverse reactions were compared before and after treatment and between the two groups.RESULTS Before treatment and 1-mo post-treatment,there was no statistically significant difference in the estimated BCVA in both groups(P>0.05).BCVA decreased in the Compaq group 3 mo after treatment,and the difference was statistically significant(P<0.05).Before treatment,and 1 mo and 3 mo post-treatment,there was no statistically significant difference in the estimated IOP in either group(P>0.05).Before treatment and 1-mo post-treatment,there was no statistically significant difference in the estimated CMT,SFCT,or FAZ in either group(P>0.05).CMT and SFCT values decreased in the Compaq group 3 mo post-treatment,and the difference was statistically significant(P<0.05).Before treatment,and 1 mo and 3 mo post-treatment,there were no statistically significant differences in vascular density in the shallow or deep capillary plexi of the fovea,parafovea,or overall macular area between the two groups(P>0.05).Marked efficient,effective,and invalid rates were 70.83%and 52.08%,27.08%and 39.58%,and 2.08%and 8.33%in the Compaq and ranibizumab groups,respectively.The differences between the two groups were statistically significant(P<0.05).CONCLUSION Anti-VEGF drugs can effectively improve CMT and SFCT,without affecting microcirculation,thus providing an effective and safe treatment for patients with DME.

Antitumor and antiangiogenic activities of anti-vascular endothelial growth factor hairpin ribozyme in human hepatocellular carcinoma cell cultures and xenografts

AIM: To study the effectiveness and mechanisms of anti-human vascular endothelial growth factor (hVEGF) hairpin ribozyme on angiogenesis,oncogenicity and tumor growth in a hepatocarcinoma cell line and a xenografted model. METHODS: The artificial anti-hVEGF hairpin ribozyme was transfected into hepatocarcinoma cell line SMMC-7721 and,subsequently,polymerase chain reaction (PCR) and reverse transcription polymerase chain reaction (RT-PCR) were performed to confirm the ribozyme gene integration and transcription. To determine the effects of ribozyme ,VEGF expression was detected by semiquantitative RT-PCR and enzyme liked immunosorbent assay (ELISA). MTT assay was carried out to measure the cell proliferation. Furthermore,the transfected and control cells were inoculated into nude mice respectively,the growth of cells in nude mice and angiogenesis were observed. RESULTS: VEGF expression was down-regulated sharply by ribozyme in transfected SMMC-7721 cells and xenografted tumor. Compared to the control group,the transfected cells grew slower in cell cultures and xenografts,and the xenograft formation was delayed as well. In addition,the microvessel density of the xenografted tumor was obviously declined in the transfected group. As demonstratedby microscopy,reduction of VEGF production induced by ribozyme resulted in a significantly higher cell differentiation and less proliferation vigor in xenografted tumor. CONCLUSION: Anti-hVEGF hairpin ribozyme can effectively inhibit VEGF expression and growth of hepatocarcinoma in vitro and in vivo. VEGF is functionally related to cell proliferation,differentiation and tumori-genesis in hepatocarcinoma.

Combined therapy versus anti-vascular endothelial growth factor monotherapy for polypoidal choroidal vasculopathy： a Meta-analysis

AIM： To evaluate the efficacy and safety of anti-vascular endothelial growth factor （VEGF） combined with photodynamic therapy （PDT） versus anti-VEGF monotherapy for polypoidal choroidal vasculopathy （PCV）. METHODS： We conducted a Meta-analysis of 9 studies to compare the efficacy and safety between combined therapy and anti-VEGF monotherapy for PCV. The programs of RevMan 5.3 and Stata 12.0 were used to analyze data. RESULTS： The best corrected visual acuity （BCVA） in combined therapy group were significantly better than those of anti-VEGF monotherapy group at 6, 24 and 36mo, with pooled weighted means differences （WMDs） of 0.12 （0.06, 0.18）, 0.25 （0.12, 0.38） and 0.28 （0.13, 0.43）, respectively. The central retinal thickness （CRT） reductions in combined therapy group were higher than that in anti- VEGF monotherapy group at 1, 3, 6 and 9mo, with pooled WMDs of 63.90 （20.41, 107.38）, 33.47 （4.69, 62.24）, 30.57 （0.12, 60.01） and 28.00 （2.51, 53.49）, respectively. The regression rate of polyps in combined therapy group was much higher than that in anti-VEGF monotherapy group [RD： 0.47 （0.26, 0.68）; P〈0.0001]. The adverse event retinal hemorrhage did not differ significantly between the two groups. CONCLUSION： Our findings clearly document that anti- VEGF combined with PDT is a more effective therapy for PCV compared with anti-VEGF monotherapy. Furthermore, combined therapy does not increase the incidence of retinal hemorrhage.

Anti-vascular endothelial growth factor treatment for retinopathy of prematurity

Retinopathy of prematurity(ROP)is a proliferative disorder of the developing retina in premature and low birth weight infants.Recently,the role of vascular endothelial growth factor(VEGF)in the pathophysiology of ROP has been well studied and anti-VEGF drugs have been used in phase 2 to treat ROP patients in many ways.At first,ophthalmologists began to give intravitreal bevacizumab(IVB)or ranibizumab off-label to treat ROP as a salvage treatment after failure in laser photocoagulation or in combination with laser as an adjuvant treatment for patients had media opacity or rigid pupil.Now anti-VEGF drugs are also used as monotherapy in type I ROP or perioperative use in stage 4/5 ROP.Questions remain regarding long-term safety,dose,timing,visual outcomes and long-term effects,including systemically.

Does Anti-Vascular Endothelial Growth Factor Treatment Delay Photoreceptor Maturation in Preterm Infants?

Purpose: To investigate the effects of intravitreal anti-vascular endothelial growth factor (VEGF) for treatment of type-1 or aggressive posterior retinopathy of prematurity (ROP) on photoreceptor maturation in preterm infants using spectral domain optical coherence tomography (SD-OCT). Methods: A study group of 36 patients with ROP treated with anti-VEGF therapy was compared to a control group of 80 patients with ROP. All patients had undergone SD-OCT imaging at least once between 40 and 44 weeks post-menstrual age (PMA). Two imaging specialists evaluated the images for ellipsoid zone (EZ) development, cystoid macular edema (CME), sub-retinal fluid (SRF) at the fovea, and cone outer segment tips (COST). The outer nuclear layer thickness and the distance from the EZ to the central fovea was measured. Results: EZ development was observed in 18 (50%) patients in the study group and 68 (85%) in the control group (p = 0.002). CME was observed in 17 (47.2%) patients in the study group and 17 (21.2%) in the control group. The distance between the EZ and central fovea was 868 ± 440 μm in the study group and 725 ± 380 μm in the control group (p = 0.02). COST was not observed in any patient. Regression analysis indicated that anti-VEGF treatment and CME affect EZ development. Conclusions: Early photoreceptor maturation is correlated with preterm birth week but not ROP stage. Anti-VEGF treatment delays photoreceptor maturation in preterm infants.

Vascular endothelial growth factor/connective tissue growth factor and proteomic analysis of aqueous humor after intravitreal conbercept for proliferative diabetes retinopathy

AIM:To investigate the role of connective tissue growth factor(CTGF)and vascular endothelial growth factor(VEGF)in the protein profile of the aqueous humor in patients with proliferative diabetic retinopathy(PDR)following intravitreal injection of conbercept.METHODS:This study included 72 PDR patients and 8 cataract patients as controls.PDR patients were divided into 3 groups according to the intervals of 3,5,and 7d between intravitreal conbercept(IVC,0.5 mg/0.05 mL)injection and pars plana vitrectomy(PPV)performed.Aqueous humor samples were collected before and after IVC and PPV for VEGF and CTGF levels detected with enzyme-linked immunosorbent assay(ELISA).The differential proteomics of 10 patients who underwent PPV surgery 5d after IVC and 8 normal controls was studied,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were performed on the data,and the protein interaction network of 23 differential proteins was studied.RESULTS:Post-IVC,VEGF levels decreased and CTGF levels increased significantly in aqueous humor,with the CTGF/VEGF ratio rising significantly at all intervals.Liquid chromatography tandem mass spectrometry(LC-MS/MS)identified differentially expressed proteins between preand post-IVC samples.GO and KEGG analyses revealed involvement in immune response,stress response,complement and coagulation cascades,ferroptosis,and PPAR signaling pathways.PPI analysis highlighted key proteins like APOA1,C3,and transferrin(TF).ELISA assay confirmed the differential expression of proteins such as HBA1,SERPINA1,COL1A1,and ACTB,with significant changes in the IVC groups.CONCLUSION:The study demonstrates that IVC effectively reduces VEGF levels while increasing CTGF levels,thereby modifying the CTGF/VEGF ratio,and IVC significantly alters the protein profile in the aqueous humor of patients with PDR.Proteomic analysis reveals that these changes are associated with critical biological pathways and protein interactions involved in immune response,stress response,and cellular metabolism.

Expression and significance of pigment epithelium-derived factor and vascular endothelial growth factor in colorectal adenoma and cancer

BACKGROUND The incidence and mortality of colorectal cancer(CRC)are among the highest in the world,and its occurrence and development are closely related to tumor neovascularization.When the balance between pigment epithelium-derived factors(PEDF)that inhibit angiogenesis and vascular endothelial growth factors(VEGF)that stimulate angiogenesis is broken,angiogenesis is out of control,resulting in tumor development.Therefore,it is very necessary to find more therapeutic targets for CRC for early intervention and later treatment.AIM To investigate the expression and significance of PEDF,VEGF,and CD31-stained microvessel density values(CD31-MVD)in normal colorectal mucosa,adenoma,and CRC.METHODS In this case-control study,we collected archived wax blocks of specimens from the Digestive Endoscopy Center and the General Surgery Department of Chengdu Second People's Hospital from April 2022 to October 2022.Fifty cases of specimen wax blocks were selected as normal intestinal mucosa confirmed by electronic colonoscopy and concurrent biopsy(normal control group),50 cases of specimen wax blocks were selected as colorectal adenoma confirmed by electronic colonoscopy and pathological biopsy(adenoma group),and 50 cases of specimen wax blocks were selected as CRC confirmed by postoperative pathological biopsy after inpatient operation of general surgery(CRC group).An immunohistochemical staining experiment was carried out to detect PEDF and VEGF expression in three groups of specimens,analyze their differences,study the relationship between the two and clinicopathological factors in CRC group,record CD31-MVD in the three groups,and analyze the correlation of PEDF,VEGF,and CD31-MVD in the colorectal adenoma group and the CRC group.The F test or adjusted F test is used to analyze measurement data statistically.Kruskal-Wallis rank sum test was used between groups for ranked data.The chi-square test,adjusted chi-square test,or Fisher's exact test were used to compare the rates between groups.All differences between groups were compared using the Bonferroni method for multiple comparisons.Spearman correlation analysis was used to test the correlation of the data.The test level(α)was 0.05,and a two-sided P<0.05 was considered statistically significant.RESULTS The positive expression rate and expression intensity of PEDF were gradually decreased in the normal control group,adenoma group,and CRC group(100%vs 78%vs 50%,χ^(2)=34.430,P<0.001;++~++vs+~++vs-~+,H=94.059,P<0.001),while VEGF increased gradually(0%vs 68%vs 96%,χ^(2)=98.35,P<0.001;-vs-~+vs++~+++,H=107.734,P<0.001).In the CRC group,the positive expression rate of PEDF decreased with the increase of differen-tiation degree,invasion depth,lymph node metastasis,distant metastasis,and TNM stage(χ^(2)=20.513,4.160,5.128,6.349,5.128,P<0.05);the high expression rate of VEGF was the opposite(χ^(2)=10.317,13.134,17.643,21.844,17.643,P<0.05).In the colorectal adenoma group,the expression intensity of PEDF correlated negatively with CD31-MVD(r=-0.601,P<0.001),whereas VEGF was not significantly different(r=0.258,P=0.07).In the CRC group,the expression intensity of PEDF correlated negatively with the expression intensity of CD31-MVD and VEGF(r=-0.297,P<0.05;r=-0.548,P<0.05),while VEGF expression intensity was positively related to CD31-MVD(r=0.421,P=0.002).CONCLUSION It is possible that PEDF can be used as a new treatment and prevention target for CRC by upregulating the expression of PEDF while inhibiting the expression of VEGF.

Transforming growth factor-β1 and vascular endothelial growth factor levels in senile acute myeloid leukemia and correlation with prognosis

BACKGROUND Acute myeloid leukemia(AML)is a disease in which immature hematopoietic cells accumulate in the bone marrow and continuously expand,inhibiting hematopoiesis.The treatment and prognosis of this disease have always been unsatisfactory.AIM To investigate the correlation between vascular endothelial growth factor(VEGF)and transforming growth factor-β1(TGFβ1)expression and prognosis in older adults with AML.METHODS This study enrolled 80 patients with AML(AML group),including 36 with complete response(AML-CR),23 with partial response(AML-PR),and 21 with no response(AML-NR).The expression levels of VEGF and TGFβ1 were detected by reverse transcription polymerase chain reaction in bone marrow mononuclear cells isolated from 56 healthy controls.Kaplan-Meier analysis was performed to assess overall survival(OS)and progression-or disease-free survival(DFS).Prognostic risk factors were analyzed using a Cox proportional hazards model.RESULTS The AML group showed a VEGF level of 2.68±0.16.VEGF expression was lower in patients with AML-CR than those with AML-PR or AML-NR(P<0.05).TGFβ1 expression in the AML group was 0.33±0.05.Patients with AML-CR showed a higher TGFβ1 expression than those with AML-PR or AML-NR(P<0.05).VEGF and TGFβ1 expression in patients with AML was significantly correlated with the counts of leukocytes,platelets,hemoglobin,and peripheral blood immature cells(P<0.05);Kaplan-Meier survival analysis revealed that patients with high TGFβ1 expression had better OS and DFS than those with low TGFβ1 expression(P<0.05),whereas patients with low VEGF levels showed better OS and DFS than those with high VEGF levels(P<0.05).VEGF,TGFβ1,and platelet count were identified by the Cox proportional hazards model as independent risk factors for OS(P<0.05),while VEGF,TGFβ1,and white blood cell count were independent risk factors for DFS(P<0.05).CONCLUSION Decreased VEGF expression and increased TGFβ1 expression in patients with AML provide valuable references for determining and individualizing clinical treatment strategies.

Hypoxia-inducible factor 1alpha and vascular endothelial growth factor in Glioblastoma Multiforme:a systematic review going beyond pathologic implications

Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation.Hypoxic conditions in the tissue microenvironment are considered a pivotal player leading tumor progression.Specifically,hypoxia is known to activate inducible factors,such as hypoxia-inducible factor 1alpha(HIF-1α),which in turn can stimulate tumor neo-angiogenesis through activation of various downward mediators,such as the vascular endothelial growth factor(VEGF).Here,we aimed to explore the role of HIF-1α/VEGF immunophenotypes alone and in combination with other prognostic markers or clinical and image analysis data,as potential biomarkers of GBM prognosis and treatment efficacy.We performed a systematic review(Medline/Embase,and Pubmed database search was completed by 16th of April 2024 by two independent teams;PRISMA 2020).We evaluated methods of immunoassays,cell viability,or animal or patient survival methods of the retrieved studies to assess unbiased data.We used inclusion criteria,such as the evaluation of GBM prognosis based on HIF-1α/VEGF expression,other biomarkers or clinical and imaging manifestations in GBM related to HIF-1α/VEGF expression,application of immunoassays for protein expression,and evaluation of the effectiveness of GBM therapeutic strategies based on HIF-1α/VEGF expression.We used exclusion criteria,such as data not reporting both HIF-1αand VEGF or prognosis.We included 50 studies investigating in total 1319 GBM human specimens,18 different cell lines or GBM-derived stem cells,and 6 different animal models,to identify the association of HIF-1α/VEGF immunophenotypes,and with other prognostic factors,clinical and macroscopic data in GBM prognosis and therapeutic approaches.We found that increased HIF-1α/VEGF expression in GBM correlates with oncogenic factors,such as miR-210-3p,Oct4,AKT,COX-2,PDGF-C,PLDO3,M2 polarization,or ALK,leading to unfavorable survival.Reduced HIF-1α/VEGF expression correlates with FIH-1,ADNP,or STAT1 upregulation,as well as with clinical manifestations,like epileptogenicity,and a favorable prognosis of GBM.Based on our data,HIF-1αor VEGF immunophenotypes may be a useful tool to clarify MRI-PET imaging data distinguishing between GBM tumor progression and pseudoprogression.Finally,HIF-1α/VEGF immunophenotypes can reflect GBM treatment efficacy,including combined first-line treatment with histone deacetylase inhibitors,thimerosal,or an active metabolite of irinotecan,as well as STAT3 inhibitors alone,and resulting in a favorable tumor prognosis and patient survival.These data were supported by a combination of variable methods used to evaluate HIF-1α/VEGF immunophenotypes.Data limitations may include the use of less sensitive detection methods in some cases.Overall,our data support HIF-1α/VEGF’s role as biomarkers of GBM prognosis and treatment efficacy.

Vascular endothelial growth factor pathway’s influence on bevacizumab efficacy in metastatic colorectal cancer treatment

In this article,an article published in the World Journal of Gastrointestinal Oncology,which focuses on whether the expression of programmed death-ligand 1(PD-L1)affects the effectiveness of chemotherapy regimens,including bevacizumab,in treating patients with colorectal cancer(CRC).Through neutralization of vascular endothelial growth factor(VEGF),bevacizumab inhibits tumor angiogenesis,impairing neovascularization and thereby depriving the tumor of essential nutrients and oxygen.Conversely,PD-L1 binding to VEGF receptor 2 promotes angiogenesis,supporting tumor vasculature.The interplay between these pathways complicates the assessment of bevacizumab’s efficacy in cancer therapy,notably in CRC,where VEGF and PD-L1 significantly affect treatment response.This review examines metastatic CRC treatment strategies,focusing on bevacizumab’s mechanism of action and the role of PD-L1 in this therapeutic context.

Diagnostic value of serum vascular endothelial growth factor and interleukin-17 in primary hepatocellular carcinoma

BACKGROUND Despite significant advancements in the medical treatment of primary hepato-cellular carcinoma(PHC)in recent years,enhancing therapeutic effects and im-proving prognosis remain substantial challenges worldwide.AIM To investigate the expression levels of serum vascular endothelial growth factor(VEGF)and interleukin(IL)-17 in patients with PHC and evaluate their diagnostic value while exploring their relationship with patients’clinical characteristics.METHODS The study included 50 patients with confirmed PHC who visited Wuhan Han-yang Hospital from January 2021 to January 2022,and 50 healthy individuals from the same period served as the control group.Serum VEGF and IL-17 levels in both groups were measured by Enzyme-Linked Immunosorbent Assay,and their diagnostic value was assessed using receiver operating characteristic(ROC)curves.Pearson correlation analysis was performed to examine the relationship between serum VEGF and IL-17 levels.Pathological data of the PHC patients were analyzed to determine the relationship between serum VEGF and IL-17 levels and pathological characteristics.RESULTS Serum VEGF and IL-17 levels were significantly higher in the study group com-pared to the control group(P<0.05).No significant association was observed between serum VEGF and IL-17 levels and gender,age,combined cirrhosis,tumor diameter,or degree of differentiation(P>0.05).However,there was a significant relationship between clinical TNM stage,tumor metastasis,and serum VEGF and IL-17 levels(P<0.05).Correlation analysis revealed a positive correlation between serum VEGF and IL-17(P<0.05).ROC analysis demonstrated that both serum VEGF and IL-17 had good diagnostic efficacy for PHC.CONCLUSION Serum VEGF and IL-17 levels were significantly higher in PHC patients compared to healthy individuals.Their levels were closely related to pathological features such as tumor metastasis and clinical TNM stage,and there was a significant positive correlation between VEGF and IL-17.These biomarkers may serve as valuable reference in-dicators for the early diagnosis and treatment guidance of PHC.

Safety and efficacy of intravitreal anti vascular endothelial growth factor for severe posterior retinopathy of prematurity with flat fibrovascular proliferation

BACKGROUND Intravitreal anti-vascular endothelial growth factor(IVA)injection is known to cause contraction of fibrovascular proliferation(FVP),when present in severe retinopathy of prematurity(ROP).AIM To assess the structural outcomes of IVA injection in the treatment of severe posterior ROP with significant FVP.METHODS It was a retrospective study in which 36 eyes of 18 preterm babies who developed>4 clock hours of FVP in zone I or posterior zone II,were treated with either intravitreal 0.625 mg bevacizumab or intravitreal 0.2 mg of ranibizumab.Favorable structural outcome included resolution of plus disease and FVP without the development of tractional retinal detachment.Secondary outcome measure included either full retinal maturation at follow-up or development of recurrent disease requiring additional treatment.Adverse outcomes included progression to retinal detachment.RESULTS The mean gestational age of the 18 preterm babies was 30 wk(range 27-36),and mean birth weight was 1319 g(range 650-1980 g).Mean post-menstrual age(PMA)at the time of primary treatment was 35.5 wk(range 31-41 wk).All eyes showed regression of plus disease and FVP.5 eyes of 3 babies showed reactivation of disease and were treated with repeat IVA(n=2 eyes)or peripheral laser photocoagulation(n=3 eyes)respectively.16 out of 36(44%)reached retinal vascular maturation at final follow up at 5 years.CONCLUSION There was good resolution of severe posterior ROP with FVP with IVA,with retinal maturity of 44%at 5 year follow-up and a reactivation rate of 13.8%.When the IVA injection is given prior to 37 wk PMA,while disease is in phase 2,it is less likely to cause contracture of pre-existing FVP.

Progress of anti-vascular endothelial growth factor therapy for ocular neovascular disease： benefits and challenges

publication. Study selection Clinical trials and case studies presented at medical conferences and published in peer-reviewed literature in the past decade were reviewed. Results Anti-VEGF agents have manifested great potential and promising outcomes in treating ocular neovascularization, though some of them are still used as off-label drugs. Intravitrea~ injection of anti-VEGF agents could be accompanied by devastating ocular or systemic complications, and intimate monitoring in both adult and pediatric population are warranted. Future directions should be focused on carrying out more well-designed large-scale controlled trials, promoting sustained duration of action, developing safer and more efficient generation of anti-VEGF agents. Conclusions Anti-VEGF treatment has proved to be beneficial in treating both anterior and posterior neovascular ocular diseases. However, more safer and affordable antiangiogenic agencies and regimens are warranted to be explored.

An efficacy analysis of anti-vascular endothelial growth factor therapy for choroidal neovascularization secondary to multifocal choroiditis and comparison with wet age-related macular degeneration

Objective： To evaluate the effect of anti-vascular endothelial growth factor （VEGF） on juxtafoveal choroidal neovascularization （CNV） secondary to multifocal choroiditis （MFC） and wet age-related macular degeneration （AMD）. Methods： In this retrospective, comparative study, 20 unique eyes with CNV were divided into two groups： 10 patients affected by MFC and 10 patients diagnosed with wet AMD. They all received local intravitreal （Ivr） injections of ranibizumab, with 6 months of follow-up. Retreatment injections were performed based on findings suggestive of active neovascularization. Results： Significant improvements were observed in the juxtafoveal CNV lesions, and average central macular thickness decreased in both groups following the anti-VEGF therapy （P〈0.05）. The average number of injections used in MFC patients was 1.6, while three injections on average were used in wet AMD patients （Z=-2.844, P=0.009）. Best-corrected visual acuity was significantly improved in MFC patients after anti-VEGF therapy （P〈0.05）, and there was no significant difference in wet AMD patients between before anti-VEGF therapy and 6 months later （P〉0.05）. Conclusions： IVT ranibizumab resulted in good clinical outcomes for juxtafoveal CNV secondary to MFC and wet AMD, but the average number of injections used in MFC was fewer than that used in wet AMD over a 6-month observation period. Compared with the wet AMD group, visual acuity was obviously improved in the MFC group at 6 months.