Conbercept Group Research Articles

Effect and factors associated with reactivation after intravitreal conbercept or aflibercept in retinopathy of prematurity

BackgroundTo evaluate the effect and factors associated with the reactivation of retinopathy of prematurity (ROP) after intravitreal conbercept or aflibercept.MethodsWe retrospectively reviewed the medical records of 176 eyes diagnosed with ROP and treated with anti-VEGF therapy between January 2018 and September 2022. The rate of reactivation and complications were assessed during the follow-up period. The factors of reactivation of ROP after intravitreal conbercept or aflibercept were analyzed on the basis of clinical factors and retinal parameters.ResultsReactivation of ROP occurred in 10 eyes (13.9%) after intravitreal conbercept and 13 eyes (12.5%) after intravitreal aflibercept (P = 0.79). The interval between injection and reactivation was significantly longer in the aflibercept group than in the conbercept group (15.50 ± 4.05 vs. 5.36 ± 0.50 weeks) (P < 0.001). The central retinal arteriolar equivalent (CRAE) of aggressive ROP was larger than that of type 1 prethreshold and threshold ROP before anti-VEGF therapy (P < 0.05). Zone I and stage 3 exhibited a positive correlation with the reactivation of retinopathy of prematurity (ROP) [odds ratio (OR) = 20.15, 5.02]. The changes in CRAE of pre-and post-therapy and gestational age were identified as potential protective factors for these outcomes (OR = 0.23, 0.49).ConclusionsConbercept and aflibercept are effective for treating ROP. Aflibercept resulted in longer treatment intervals compared to conbercept. Zone, stage, and gestational age were associated with the reactivation of ROP. CRAE was associated with not only the severity of ROP but also its reactivation. Additionally, it may be an objective indicator in the early indication and follow-up of ROP.

VEGFA may be a potential marker of myopic choroidal thickness and vascular density changes

To evaluate the changes of choroidal thickness (CT) and blood flow related to myopia, and its effects of vascular endothelial growth factor (VEGFA) on choroidal vessels in myopia. Subjects were included and divided into emmetropia (EM), non-high myopia (Non-HM) and high myopia (HM) groups. we measured choroidal thickness (CT), choriocapillaris vessel density (VD), and VEGFA content in tears in humans (137 subjects for CT, VD and 84 for tear) and detected the role of VEGFA in the choroid in form-deprivation myopia (FDM) in guinea pigs. Twenty-four guinea pigs were divided into control and FDM groups, and the expression changes of choroidal vessels and VEGFA were observed and compared using immunohistochemistry and Western blotting. Twenty-one guinea pigs were divided into control, FDM + Vehicle and FDM + Conbercept groups. The changes of diopter, axis length and choroidal vessels after intravitreal injection of Conbercept were observed. There were significant differences in CT and VD among the three groups (p < 0.05). VEGFA levels in tears were significantly lower in the myopic groups, with a decreasing trend from EM to Non-HM to HM. The choroidal vascular area fraction of FDM decreased compared to the control group. FDM guinea pigs exhibited reduced choroidal vasculature and significant downregulation of VEGFA expression. Following intravitreal injection of conbercept, the FDM + Conbercept group showed greater myopia, longer axial length, and lower choroidal vascular area fraction compared to the control group. VEGFA may participate in the regulation of choroidal blood vessels and blood flow in the progression of myopia. The reduction in VEGFA may accelerates the progression of myopia.

Conbercept reverses TGF-β2-induced epithelial-mesenchymal transition in human lens epithelial cells by regulating the TGF-β/Smad signaling pathway

To investigate the mechanism by which conbercept reverses transforming growth factor-β2 (TGF-β2)-induced epithelial-mesenchymal transition (EMT) in human lens epithelial cells (HLECs). Cultured HLEC SRA01/04 cells were treated with TGF-β2, conbercept, or both, and the changes in cell proliferation, apoptosis, and migration were observed using MTT assay, flow cytometry, scratch assay, and Transwell assay. Western blotting and qRT-PCR were used to detect the changes in the expression of EMT-related epithelial cell markers (E-Cadherin, α-SMA, and Snail), extracellular matrix components, and genes related to the TGF-β/Smad signaling pathway. Conbercept significantly reduced TGF-β2-induced EMT of SRA01/04 cells, decreased the expression levels of mesenchymal and extracellular matrix markers α-SMA, Snail, collagen I, collagen IV, and FN1, and upregulated the protein and mRNA expressions of E-cadherin (P <0.05). Transwell assay showed significantly lower cell migration ability in TGF-β2+conbercept group than in TGF-β2 group (P <0.05). Conbercept also inhibited the increase in Smad2/3 phosphorylation levels in HLEC-SRA01/04 cells with TGF-β2-induced EMT (P <0.01). Conbercept inhibits TGF-β2 induced EMT by downregulating the expression of pSmad2/3 in TGF-β/Smad signaling pathway, indicating a potential therapeutic strategy against visual loss induced by posterior capsule opacification.

Intravitreal Injection of Conbercept Combined with Dexamethasone for Macular Edema Following Central Retinal Vein Occlusion.

To compare the efficacy of intravitreal injections of Conbercept combined with dexamethasone (DEX) for macular edema (ME) following central retinal vein occlusion (CRVO). This was a prospective, single-masked, randomised, controlled clinical trial. Patients with ME following CRVO were randomised into groups to receive intravitreal injections of 0.5 mg Conbercept plus 0.2 mg DEX or 0.5 mg Conbercept alone on day 0 followed by repeat injections as indicated. The primary outcome measure was the change in best-corrected visual acuity (BCVA) from baseline to month 12. Secondary outcome measures included decrease in central retinal thickness (CRT), injection frequency and interval and percentage of patients who gained more than 15 ETDRS letters or achieved a CRT of < 250 μm at month 12. 33 males (51%) and 32 females (49%) were initially recruited with an average age of 56.64 ± 13.88 years. Patients in the Conbercept and Conbercept + DEX groups gained an average of 14.55 ± 19.19 and 14.88 ± 17.68 ETDRS letters, respectively, at months 12 (t = 4.221, P = 0.000; and t = 4.834, P = 0.000) with no significant difference between the two groups (t = 0.071, P = 0.943). In the Conbercept group, the mean reduction in CRT from baseline to month 12 was 435.26 ± 293.37 μm (t = 8.261, P = 0.000) compared to 431.36 ± 294.55 (t = 8.413, P = 0.000) in the Conbercept + DEX group. There was no significant difference between the two groups (t = 0.053, P = 0.958). The Conbercept + DEX group received fewer intravitreal injections. No major complications occurred. Conbercept, alone or with DEX, can improve BCVA and reduce CRT in ME following CRVO without serious adverse events. The treatment interval was longer in the Conbercept + DEX group. The study was registered with the Chinese Clinical Trial Registry at 5 July 2017. (http://www.chictr.org.cn, 05/07/2017 Registration Number: ChiCTR-INR-17011877).

Retrospective analysis of the etiology and drugs for vitreous hemorrhage caused by non-diabetic retinopathy and non-traumatic factors.

To retrospectively analyze the etiology of non-diabetic retinopathy (DR) and non-traumatic vitreous haemorrhage (VH), and the effects of different anti-vascular endothelial growth factor (VEGF) drugs. A retrospective analysis was conducted on VH patients diagnosed as non-diabetic retinopathy or trauma. Among 101 patients treated with anti-VEGF drugs, there were 48 cases in the Conbercept group and 53 cases in the Ranibizumab group. The causes of bleeding and gender distribution of the included cases were analyzed. In cases of retinal vein occlusion, the proportion of males was much higher than females (p < 0.05). After treatment, the best corrected visual acuity (BCVA), intraocular pressure, central macular thickness (CMT), aqueous humor VEGF, TNF-α, IL-10, and IL-6 of the two groups showed a decreasing trend (p < 0.05). The Conbercept group had markedly lower CMT than the Ranibizumab group (p < 0.05). In addition, there existed no significant statistical differences between the two groups in terms of BCVA, intraocular pressure, aqueous humor VEGF, TNF-α, IL-10, IL-6, incidence of adverse reactions, and recurrence rate (p > 0.05). In patients with non-DR and traumatic VH, retinal vein occlusion, perivenous retinitis, retinal tears/detachment, exudative AMD, and polypoidal choroidal vasculopathy were the main etiologies. Conbercept and Ranibizumab had comparable efficacy and could effectively improve visual acuity and aqueous humor inflammation, with high safety and low recurrence rate. Conbercept had a more pronounced effect on the reduction of CMT in patients.

Safety and efficacy of intravitreal injection of conbercept for the treatment of patients with choroidal neovascularization secondary to pathological myopia: Results from the SHINY study.

To evaluate the safety and efficacy of intravitreal injections of 0.5 mg conbercept in patients with choroidal neovascularization secondary to pathological myopia (pmCNV). The 177 pmCNV patients were randomly assigned in a 3:1 ratio to receive conbercept or sham injection, respectively. The conbercept group receive conbercept intravitreal injections administered on a pro re nata (PRN) basis after 3 monthly loading doses. The sham group received three consecutive monthly sham injections and then one conbercept injection followed by PRN conbercept intravitreal injections. At month 3, the mean BCVA for the two groups were improved by 12.0 letters (conbercept group, from 54.05 letters to 66.05 letters) and 0.6 letters (sham group, from 49.77 letters to 50.33 letters), respectively (p < 0.001). The mean central retinal thickness (CRT) at month 3 in the two groups decreased 62.0 μm (conbercept group, from 348.90 μm to 286.18 μm) and 4.4 μm (sham group, from 347.86 μm to 343.47 μm) (p < 0.001). At month 9, the mean BCVA improved by 13.3 letters in the conbercept group and 11.3 letters in the sham group. The mean CRT decreased 73.6 μm in the conbercept group and 55.9 μm in the sham group (p < 0.001). The most common ocular adverse events were associated with intravitreal injections, such as conjunctival haemorrhage and increased intraocular pressure. Intravitreal injections of 0.5 mg conbercept provided improvement in visual and anatomical outcomes in pmCNV patients with low rates of ocular and nonocular safety events.

Study on the effects of different anti-VEGF drugs on fibrovascular membranes of proliferative diabetic retinopathy

PurposeTo investigate the effects of different anti-VEGF drugs on fibrovascular membranes (FVM) in proliferative diabetic retinopathy (PDR). In addition, in vitro model was used to simulate the intraocular fibroblasts barrier to explore the penetration of different anti-VEGF drugs. Methods24 eyes from 24 PDR patients with FVM were recruited for this prospective observational study. The patients were randomized to receive one of three anti-VEGF drugs (Ranibizumab, Conbercept, or Aflibercept). Then neovascular structures were assessed by optical coherence tomography angiography (OCTA) before intravitreal injection (pre-IVT) and 1, 2, and 3 days after intravitreal injection (post-IVT). The changes in vessels area (VSA), vessels percentage area (VPA), junction density (JD), and average lacunarity (AL) were analyzed by using the image processing software Angiotool. In vitro penetrating model with fibroblasts barrier was used to compare the effects of the three drugs on human retinal vascular endothelial cells (HRVECs) over 3 days by Cell proliferation measurement. Moreover, the drug concentrations in the penetrating model were detected by liquid chromatography-mass spectrometry (LC-MS). ResultsThe VSA, VPA, and JD all decreased, while the AL increased in Ranibizumab group(n = 8), Conbercept group (n = 8), and Aflibercept group (n = 8) within 3 days (P<0.05). Meanwhile, under the condition of the same amount of substance, the inhibition effect of Ranibizumab on HRVEC was the strongest in the penetrating model evaluated by CCK8 absorbance experiments of HRVECs (FCCK8=6.493, PCCK8= 0.0051), and the number of transmembrane molecules in the Ranibizumab group was also the largest within 3 days (F = 8.209, P = 0.0006) among the three groups. ConclusionAngiotool is feasible to reconstruct the neovascular structure on the FVM in OCTA images. The three different anti-VEGF drugs can significantly reduce the vascular area and density on the proliferating membranes, and there is no significant difference in the anti-neovascularization among the three drugs clinically. However, small molecule drug is more penetrating and move faster across membranes in vitro cell model. Clinical Trial RegistrationThis trial is registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn, registration number ChiCTR2300067476).

Changes in Serum Concentrations of Vascular Endothelial Growth Factors-A and B after Intravitreal Injection of Ranibizumab and Conbercept for Retinopathy of Prematurity

Introduction: The aim of this study was to compare the changes in serum concentrations of vascular endothelial growth factor (VEGF)-A and B after intravitreal injection of ranibizumab (IVR) or conbercept (IVC) for retinopathy of prematurity (ROP). Methods: In this prospective study, infants with type 1 ROP in both eyes were recruited in our hospital from September 2021 to February 2022, randomly assigned to the ranibizumab and conbercept groups and administered IVR or IVC (0.25 mg/0.025 mL). Blood samples were collected before the operation and 1 and 4 weeks after the operation to measure the concentrations of serum VEGF-A and B. Results: A total of 20 ROP infants were randomly assigned to the ranibizumab (n = 10) and conbercept groups (n = 10). In the ranibizumab group, the serum VEGF-A concentrations before operation and 1 and 4 weeks after the operation were 73.55 ± 40.78, 11.47 ± 7.00, and 75.36 ± 30.87 pg/mL, respectively (p < 0.01). Least Significant Difference (LSD) pairwise comparison did not show any significant difference in the groups between 4 weeks postoperatively and preoperatively (p > 0.05). In the conbercept group, the serum VEGF-A concentrations before operation and 1 and 4 weeks after the operation were 86.69 ± 55.06, 14.68 ± 10.11, and 43.55 ± 57.92 pg/mL, respectively (p < 0.01). LSD comparison showed significant differences between 1 week and 4 weeks postoperatively and preoperatively (p < 0.05), but no significant differences were observed between 1 and 4 weeks postoperatively (p > 0.05). Regarding serum VEGF-B concentrations before the operation and 1 and 4 weeks after the operation, no significant differences were detected in the ranibizumab group (p > 0.05), but significant differences were observed in the conbercept group (7.26 ± 2.34, 3.09 ± 2.41, and 4.55 ± 3.37 ng/mL, respectively; p < 0.01). LSD showed significant differences between 1 or 4 weeks postoperatively and preoperatively (p < 0.05), but no significant difference was detected between 1 and 4 weeks postoperatively (p > 0.05). Conclusions: Serum VEGF-A levels in infants with ROP were suppressed after IVR or IVC but returned to preoperative levels at 4 weeks after IVR and remained lower than the preoperative levels at 4 weeks after IVC. Serum VEGF-B was not affected by IVR but was suppressed by IVC for 4 weeks.

Efficacy and Safety of Intravitreal Injection of Triamcinolone Acetonide and Conbercept for Intraocular Lens after Cataract Surgery.

Objective To investigate the effect of intravitreal injection of triamcinolone acetonide and conbercept on the efficacy and safety of diabetic macular edema (DME) after cataract intraocular lens (IOL) surgery. Methods A total of 350 patients with cataract complicated with diabetic macular edema in our hospital from January 2017 to July 2021 were randomly divided into conbercept group and triamcinolone acetonide group. Patients in the conbercept group were given intravitreal injection of conbercept during IOL surgery, and patients in the triamcinolone acetonide group were given injection of triamcinolone acetonide during surgery. Results Three months after treatment, the best-corrected visual acuity of the two groups was significantly higher than before, the corrected visual acuity of the conbercept group was more significant than the triamcinolone acetonide group, and the intraocular pressure of the triamcinolone acetonide group was higher than the conbercept group. The foveal thickness and macular volume were significantly reduced in both groups, and was reduced more in the conbercept group than in the triamcinolone acetonide group. The contents of VEGF, SDF-1, and IL-6 in both groups were significantly decreased, and the decrease was more significant in the conbercept group than in the triamcinolone acetonide group. The patients with elevated intraocular pressure, headache and vomiting, orbital swelling pain, eye swelling pain, and eye pain in the triamcinolone acetonide group were significantly higher than those in the conbercept group (P < 0.05). Conclusions Conbercept and triamcinolone acetonide has a good therapeutic effect on DME in pseudophakic eyes after cataract IOL surgery, which can reduce the degree of macular edema and improve the visual function. However, the therapeutic effect of injection therapy with conbercept is safe, the prognosis is better, and the complication rate is low.

Short-Term Efficacy in Polypoidal Choroidal Vasculopathy Patients Treated With Intravitreal Aflibercept or Conbercept.

PurposeTo compare the short-term efficacy in patients with polypoidal choroidal vasculopathy (PCV) treated using either aflibercept or conbercept.MethodsThis prospective study included 41 patients with treatment-naive PCV (42 eyes). All the patients were treated with either aflibercept or conbercept using an initial series of 3 monthly loading injections. Changes in the best-corrected logMAR visual acuity (BCVA) and anatomic outcomes were evaluated at 3 months.ResultsBCVA was improved with reduction in central choroidal thickness (CCT), central foveal thickness (CFT), and subretinal fluid (SRF) after 3 monthly loading injections in both aflibercept (IVA) and conbercept (IVC) groups. There was no significant difference in either visual or anatomic outcomes between the two groups after 3 months of treatment. However, compared with the IVC group, significantly higher BCVA improvement was observed in the patients in the IVA group with baseline BCVA better than 1. A visual outcome improved ≥3 lines in 13 patients in the IVA group (59%), and 9 patients in the IVC group (45%). A relatively high proportion of polyp regression was observed in the IVA group (63%) compared with the IVC group (55%) via OCTA.ConclusionsVisual and anatomic outcomes were significantly improved in both IVA and IVC groups, but the results suggest a potentially superior short-term response in the IVA group.

RETINAL MICROVASCULAR CHANGES IN UVEAL MELANOMA FOLLOWING CONBERCEPT INJECTION AFTER PLAQUE RADIOTHERAPY AS DETECTED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

To investigate macular microvascular characteristics imaged by optical coherence tomography angiography in patients with uveal melanoma following conbercept injections after plaque radiotherapy. Prospective comparative analysis comprising 15 patients with uveal melanoma with conbercept injections and 30 patients without conbercept injections after plaque radiotherapy by optical coherence tomography angiography. The conbercept group received intravitreal conbercept injections at the time of plaque removal, 1 month, 3 months, 6 months , 9 months and 12 months after plaque removal (total, 6 injections). The control group had no intravitreal conbercept injection. After initiation of conbercept injections, superficial retinal vascular density in the whole image and parafoveal region were significantly higher at 6 months, whereas there was no significant difference at 9 months and 12 months. In analysis of variance analysis, superficial retinal vascular density in the whole image remained stable after conbercept injections (P = 0.069), whereas the superficial retinal vascular density decreased significantly after plaque radiotherapy in the control group (P = 0.011). In multivariable linear regression, a higher superficial retinal vascular density in the whole image region at 6 months was significantly associated with intravitreal conbercept injection (P = 0.018), wider tumor base (P = 0.026), and thinner tumor thickness (P = 0.04). Optical coherence tomography angiography can provide a quantitative evaluation of early retinal microvascular changes after radiotherapy. Intravitreal conbercept treatment could partly relieve the retinal vascular damage in response to radiation therapy at early stage in patients with uveal melanoma; however, it may not be able to provide long-term positive functional outcomes.

Different effects of anti-VEGF drugs (Ranibizumab, Aflibercept, Conbercept) on autophagy and its effect on neovascularization in RF/6A cells

IntroductionChoroidal neovascularization (CNV) is the main pathological change of wet age-related macular degeneration. Anti-VEGF drugs are the most commonly used treatment for CNV. The biggest drawback of anti-VEGF drugs is the recurrence of CNV, which requires repeated therapy several times. Autophagy activation may be involved in reducing the therapeutic effect of anti-VEGF drugs. So, this study aims to elucidate the effect and mechanism of anti-VEGF drugs on endothelial autophagy and neovascularization in vitro. MethodsRF/6A cells were randomly divided into five groups: The control group, hypoxia group (1% O2, 5% CO2, 94% N2), anti-VEGF group (group1: Ranibizumab 100 μg/ml; group2: Aflibercept, 400 μg/ml; group3: Conbercept, 100 μg/ml). Autophagy-related proteins were examined by Western blot. RFP-GFP-LC3 was used to detect autophagy and autophagic flow. Subsequently, we used autophagy inhibitors (3-MA or CQ) to inhibit Conbercept induced autophagy and to observe its effect on angiogenesis in vitro. Proliferation, migration, and tube formation of endothelial cells can be used to study neovascularization in vitro. In this research, the CCK-8 assay was used to detect cell proliferation. Cell migration and tube formation were assessed by wound assay and matrix method, respectively. Flow cytometry and Tunel were used to detect cell apoptosis. Finally, the mechanism of Conbercept activated autophagy was studied. Western blot was used to detect the expression of p53 and DRAM (damage-regulated autophagy modulator), upstream activators of autophagy. ResultsThe protein levels of Beclin-1 and LC3-2/1 in Ranibizumab and Conbercept groups were significantly higher than in the hypoxia group(P < 0.05). While the expression of P62 was decreased (P < 0.05). The autophagic flux was showed the same results. However, Aflibercept showed the opposite effect on autophagy. Compared with the Conbercept group, autophagy inhibitor 3-MA or CQ can further inhibit cell proliferation and promotes cell apoptosis (P < 0.05). Conbercept significantly inhibited cell migration compared with the hypoxia group (633.08 ± 72.52 vs. 546.33 ± 24.61), while the autophagy inhibitor group (3-MA or CQ) had a more obvious inhibition effect (309.75 ± 86.36 and 263.33 ± 68.67) (P < 0.05). For tube formation, the number of tube formation was decreased significantly in the Conbercept group (32.00 ± 2.00) compared to the hypoxia group (39.00 ± 1.53) and even further reduced in 3-MA or CQ group (24.00 ± 3.61, 20.00 ± 2.65). The length of master segments in the hypoxia group was 15,668.00 ± 894.11. It was decreased in Conbercept (13,885.34 ± 730.03). In 3-MA or CQ group, the length of master segments dropped further (11,997.00 ± 433.66, 10,617.67 ± 543.21). Compare with the hypoxia group, the expression P53 and DRAM were increased in the Conbercept group (P < 0.05). Autophagy-related proteins LC-3, Beclin-1, and DRAM were inhibited by P53 inhibitor Pifithrin-α (PFTα) (P < 0.05). ConclusionRanibizumab and Conbercept can trigger the autophagy of vascular endothelial cells while Aflibercept can inhibit it. The combination of Conbercept and autophagy inhibitor can significantly inhibit the formation of angiogenesis in vitro. The mechanism of autophagy activation is related to the activation of the p53/DRAM pathway.

Comprehensive evaluation of intravitreal conbercept versus half-dose photodynamic therapy for chronic central serous chorioretinopathy.

To compare the safety and efficacy of conbercept intravitreal injection and half-dose photodynamic therapy (PDT) in treating chronic central serous chorioretinopathy (CSC). This study was retrospective. Thirty-seven patients (37 eyes) with chronic CSC received conbercept injections while 57 patients (57 eyes) were treated with half-dose PDT. All subjects were followed in 6mo. Outcome measures included change in best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), and resolution of subretinal fluid (SRF). There was no adverse event observed in either treatment group. At the 6-month follow-up, 26 eyes (70.3%) in the conbercept group and 54 eyes (94.7%) in the half-dose PDT group (P<0.05) reached full resolution of SRF. The mean logarithm of the minimum angle of resolution (logMAR) BCVA significantly improved (P<0.001) in both treatment groups with better outcome at early phase in the half-dose PDT group (2wk, 1, and 2mo, P<0.05). All subjects experienced significant CMT improvement (P<0.001) with no statistical difference between the two groups (P>0.05). The SFCT also improved in all subjects (P<0.001) with better outcome in the half-dose PDT group (P<0.05). Both intravitreal conbercept and half-dose PDT are safe to use in treating chronic CSC. By 6mo, both treatment groups are efficacious in improving BCVA, reducing CMT and SFCT, and resolving SRF in eyes with chronic CSC. Half-dose PDT may show better outcome at initial phase of treatment in chronic CSC. Longer follow-up period is necessary to study for long-term effect and safety.

Comparison of conbercept and ranibizumab combined mitomycin C-augmented trabeculectomy for neovascular glaucoma.

To compare the efficacy and security of conbercept and ranibizumab combined with trabeculectomy and panretinal photocoagulation for neovascular glaucoma (NVG). One hundred and sixty patients with NVG were randomly divided into a conbercept group comprised of 80 patients and a ranibizumab group comprised of 80 patients. The postoperative and preoperative visual acuities, intraocular pressures frequency of anti-glaucoma medications, and surgical complications were recorded. The expressions of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (FLT-1), and placenta-like growth factor (PLGF) in the aqueous humor were determined using an enzyme-linked immunosorbent assay. Examining the fundus and obtaining photographs used indirect ophthalmoscopy. Kaplan-Meier and log-rank analyses estimated the success rates. All patient follow-up periods were at 1year. The differences observed in IOP and the frequencies of anti-glaucoma medications at various follow-up time points were not statistically significant (all P > 0.05). The differences observed in both the group visual acuities at various follow-up time points were not statistically significant (P > 0.05). Rates of surgery complications were 18.75% and 25.00% in the conbercept group and ranibizumab group, respectively. The expressions of VEGF, FLT-1, and PLGF significantly decreased (all P < 0.05). The recurrence percentages were 30.00% and 36.25% after conbercept and ranibizumab treatment, respectively. The conbercept effects were similar with that of ranibizumab. Intravitreal injection of conbercept was effective for NVG treatment, which provides a new therapeutic drug for NVG treatment.

Intravitreal conbercept as an adjuvant in vitrectomy for proliferative diabetic retinopathy: a meta-analysis of randomised controlled trials.

To evaluate the efficacy of intravitreal conbercept (IVC) in pars plana vitrectomy (PPV) for patients with proliferative diabetic retinopathy (PDR). A meta-analysis of randomized control trials (RCTs) using online databases was performed. The intraoperative outcome measures were the incidence of intraoperative bleeding and endodiathermy application, and the mean surgical time. The postoperative outcome measures were mean change in best-corrected visual acuity (BCVA) from baseline, postoperative vitreous clear-up time and incidence of recurrent vitreous hemorrhage (VH). Eight RCTs were selected for meta-analysis. They included 409 eyes (215 eyes in IVC group and 194 eyes in no conbercept group). Preoperative IVC application was associated with less intraoperative bleeding and endodiathermy applications (RR = 0.34, 95% CI, 0.23-0.50, P < 0.00001, and RR = 0.26, 95% CI, 0.12-0.56, P = 0.0005) compared to no conbercept. It also shortened surgical time (WMD = -15.87, 95% CI, -22.04 to -9.69, P < 0.00001). In addition, preoperative or intraoperative IVC achieved better BCVA outcome (WMD = -0.37, 95% CI, -0.62 to -0.13, P = 0.003), shorter vitreous clear-up time postoperatively (WMD = -5.44, 95% CI, -6.31 to -4.57, P < 0.00001) and a lower rate of VH recurrence (RR = 0.45, 95% CI, 0.22-0.91, P = 0.03). IVC is an effective adjuvant in PPV for PDR, with better intraoperative and postoperative outcomes.

The Efficacy of Conbercept in Polypoidal Choroidal Vasculopathy: A Systematic Review.

Methods Thirty studies with 1308 eyes were identified and included in this study. The primary outcome measures were best-corrected visual acuity (BCVA), and secondary outcomes were optical coherence tomography characteristics and polyp regression rates. The pooled results were calculated by the random-effect or fixed-effect model according to the heterogeneity of the data. Results Despite a large standard deviation in means (SMD) improvement for BCVA and central retinal thickness (CRT) in the conbercept group, there was no statistically significant difference in the other outcomes compared to ranibizumab and aflibercept. However, there was a greater polyp regression rate in the conbercept group at 12 months. Conclusions This systematic review indicates that conbercept may achieve similar BCVA and CRT improvements as ranibizumab and aflibercept, with a superior rate of polyp regression at 12 months.

The Role of Serum Inflammation-Based Factors in Anti-Vascular Endothelial Growth Factor Treatment for Macular Edema Secondary to Retinal Vein Occlusion and Its Subtypes

Objective: The aim of this work was to evaluate the association between pretreatment inflammation-based factors and outcomes in patients with macular edema (ME) secondary to retinal vein occlusion (RVO) and its subtypes after intravitreal ranibizumab or conbercept implant. Methods: This retrospective observational study included patients who were diagnosed with ME secondary to RVO at the First Affiliated Hospital of Nanchang University between January 2017 and January 2019, and who subsequently received intravitreal anti-vascular endothelial growth factor (VEGF) treatment. Blood-based parameters were measured before treatment, and correlations between best-corrected visual acuity (BCVA) and each of 3 parameters – neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) – were analyzed to identify predictors of effective intravitreal injection treatment outcomes. Results: A total of 315 treatment-naïve eyes treated with anti-VEGF drugs for RVO-ME were retrospectively analyzed in this study. The mean PLR value was significantly different in the effective and ineffective group for RVO-ME (138.03 ± 48.61 vs. 106.79 ± 27.28), branch RVO (BRVO)-ME (216.47 ± 53.04 vs. 185.94 ± 51.47), and central RVO (CRVO)-ME (231.07 ± 66.05 vs. 196.20 ± 60.44). The cutoff value of the PLR was 97.92, the area under the curve was 0.70, and the sensitivity and specificity were 81.5 and 44.3%, respectively. The mean NLR value was significantly different in the effective and ineffective groups for RVO-ME (2.20 ± 1.40 vs. 1.92 ± 0.89), and BRVO-ME (2.01 ± 0.80 vs. 1.82 ± 0.84), but not in patients with CRVO-ME (2.51 ± 2.02 vs. 2.12 ± 0.95). There are no significant differences between BRVO-ME and its subtype groups in MLR values. But the mean MLR value was significantly higher in the conbercept group than in the ranibizu­mab group among patients in the effective group (0.27 ± 0.11 vs. 0.25 ± 0.14). Conclusion: Higher pretreatment PLR was associated with BCVA in patients with RVO-ME and its subtypes who were treated with anti-VEGF drugs. The PLR may be used as a predictive and prognostic tool for effective intravitreal injection treatment outcomes.

Effect of Jiajian-Zhujing Decoction on the AKT/mTOR signaling pathway in ARPE-19 cells after AKT transfection

Objective To study the mechanism of the effect of Jiajian-Zhujing Decoction on the expression of VEGF on ARPE-19 cells after AKT transfection. Methods To prepare the serum and blank serum of Jiajian-Zhujing Decoction and divide ARPE-19 cells into the normal group, model group, blank serum group, medicated serum group, Conbercept group and combined group. Except normal group, this research established AKT transfected cell model. Then cultured the normal group and model group with conventional method, and the blank serum group was cultured with 10% blank serum, the medicated serum group was cultured with 10% medicated serum, the Conbercept group was cultured with 20 μg/ml Conbercept, the combined group was cultured with 10% medicated serum and 20 μg/m Conbercept. The proliferation of ARPE-19 cells in each group was detect by the CCK-8 method. The levels of AKT, mTOR and VEGF mRNA were detected by real-time quantitative PCR. Western blot was used to detect the expression of AKT, mTOR and VEGF. Results After being cultured for 24, 48 and 72 hours, compared with the model group, the cell proliferation rate in blank serum group, medicated serum group, Conbercept group and combined group significantly decreased (P<0.05). Compared with the model group, the expression of AKT mRNA (24 h: 3.10 ± 0.48, 1.97 ± 0.14, 1.26 ± 0.24 vs. 4.77 ± 0.68; 48 h: 3.52 ± 0.82, 2.62 ± 0.77, 1.10 ± 0.19 vs. 6.12 ± 1.21), mTOR mRNA (24 h: 3.02 ± 0.26, 2.45 ± 0.75, 1.13 ± 0.15 vs. 4.48 ± 0.80; 48 h: 1.29 ± 0.30, 1.30 ± 0.57, 0.65 ± 0.19 vs. 2.54 ± 0.62), VEGF mRNA (24 h: 3.33 ± 0.62, 2.18 ± 0.20, 1.55 ± 0.28 vs. 5.53 ± 1.02; 48 h: 2.35 ± 0.54, 1.23 ± 0.28, 0.93 ± 0.25 vs. 3.59 ± 0.40), AKT protion (24 h: 0.45 ± 0.09, 0.25 ± 0.05, 0.14 ± 0.04 vs. 0.62 ± 0.04; 48 h: 0.36 ± 0.06, 0.23 ± 0.04, 0.14 ± 0.03 vs. 0.54 ± 0.08), mTOR protion (24 h: 0.35 ± 0.05, 0.24 ± 0.02, 0.18 ± 0.02 vs. 0.52 ± 0.09; 48 h: 0.23 ± 0.04, 0.29 ± 0.04, 0.14 ± 0.03 vs. 0.40 ± 0.10), VEGF protion (24 h: 0.14 ± 0.03, 0.33 ± 0.04, 0.24 ± 0.03 vs. 0.54 ± 0.10; 48 h: 0.24 ± 0.03, 0.17 ± 0.02, 0.11 ± 0.02 vs. 0.42 ± 0.10) significantly decreased (P<0.05), and the combined group was significantly lower than that of the Conbercept group (P<0.05). Conclusions AKT transfection can promote the proliferation of ARPE-19 cells, and Jiajian-Zhujing Decoction can significantly inhibit this proliferation. Jiajian-Zhujing Decoction may inhibit the activity of AKT/mTOR signaling pathway to reduce the expression of VEGF. Key words: Serum pharmacology (TCD); Retinal pigment epithelium; Transfection; Vascular endothelial growth factors; Jiajian-Zhujing Decoction

Intravitreal conbercept improves outcome in patients undergoing vitrectomy for proliferative diabetic retinopathy: A systematic review and meta-analysis.

To evaluate the latest evidence concerning the efficacy of conbercept on vitrectomy for proliferative diabetic retinopathy (PDR) and its efficacy compared to control and other antivascular endothelial growth factor. We performed a systematic literature search on topics that assess the role of conbercept in patients undergoing vitrectomy for PDR from inception to November 2019, using PubMed, EuropePMC, Cochrane Central Database, ProQuest, ScienceDirect, and Clinicaltrials.gov. Two researchers independently searched literature, extracted data, and evaluated the risk of bias. RevMan 5.3 and StataMP 16 software were used to perform data analysis. There were 699 cases (eyes) from eight studies. Baseline best-corrected visual acuity (BCVA) was better in the control group compared to conbercept group (mean difference [MD]=0.13, I2 =0%). A greater BCVA improvement was observed in the conbercept group after 1-month (MD=-0.27, I2 =1%), 3-month (MD=-0.28, I2 =0%), and 6-month (MD=-0.20, I2 =78%) follow-up. The need for endodiathermy (odds ratio [OR]=0.20, I2 =0%) and silicone oil tamponade use (OR=0.59, I2 =72%) and intraoperative bleeding (OR=0.11, I2 =33%) was lower in conbercept group. Postoperative early (OR=0.22, I2 =0%) and late (OR=0.47, I2 =0%) vitreous hemorrhage was lower in conbercept group. There was no significant difference in BCVA improvement and intraoperative outcome between conbercept and ranibizumab. Intravitreal conbercept was associated with a more significant BCVA improvement, better intraoperative outcome, and less postoperative vitreous hemorrhage compared to no conbercept.

Effect of multiple subconjunctival conbercept injections as an adjuvant to the surgical treatment of pterygium: a prospective randomised comparative 6-month follow-up study.

To evaluate the safety and efficacy of multiple subconjunctival injections of conbercept for pterygium patients after surgery. As a prospective randomised interventional trial, 96 eyes from 96 patients with a tendency to recur were collected and divided randomly into conbercept and 5-fluorouracil groups on the 5th day after pterygium. All patients received three subconjunctival injections of conbercept (0.2 ml) or 5-fluorouracil (0.2 ml) on the 5th day (baseline), and 2 and 4 weeks post-operatively. The pterygium morphology, colour intensity, recurrence, and complications were recorded and analysed pre-1st injection and 1 day, 1 week, 1 month, 3 months, and 6 months post-3rd injection. Moreover, no patient was drop-out. There were striking differences between the two groups on post-3rd injections 1 day, 1 week, 1 month, 3 months, and 6 months (p = 0.001, 0.002, 0.000, 0.000, and 0.002, respectively) with respect to colour intensity: the eyes in conbercept group were lighter than the 5-Fu group. On post-3rd injection 6 months, prominent disparities existed between the two groups with respect to pterygium morphology (p = 0.006) and recurrence (p = 0.002), occurred in the conbercept group prior to the 5-Fu group. Moreover, corneal abrasions were not noted in the conbercept group, which was significantly less than the 5-Fu group (17/48; p = 0.000). There was no conspicuous discrepancy between the two groups with respect to subconjunctival haemorrhage (p = 0.789) and persistent epithelial defects (p = 0.078). Multiple subconjunctival conbercept injections as an adjunct therapy for pterygium surgery was shown to be safe, effective, and well-tolerated.