Image-Guided Marking versus Manual Marking in Phacoemulsification with Toric Intraocular Lens (IOL) Implantation: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

PURPOSES: The purpose of this meta-analysis is to systematically compare the alignment accuracy and post uncorrected distance visual acuity (UDVA) between image-guided marking and manual marking for toric intraocular lens (IOL) in cataract surgery. METHODS: This work was done through the data searched from the PubMed, EMBASE and the Cochrane Library. The Cochrane Handbook was also used to evaluate the quality of the included studies. In addition, this meta-analysis was performed using Revman 5.4 software. RESULTS: A total of 6 randomized controlled trials (RCTs) were included. Compared with manual marking group, image-guided marking group had less toric IOL axis misalignment (MD, -1.98; 95%CI, -3.27 to -0.68; p = .003), less postoperative astigmatism (MD, -0.13; 95%CI, -0.21 to -0.05; p = .001), better postoperative UDVA (MD, -0.02; 95%CI, -0.04 to -0.01; p = .0003) and smaller difference vector (MD, -0.10; 95%CI, -0.14 to -0.06; p(0.00001). For the proportion of patients with residual refractive cylinder within 0.5 D, there was no difference between two groups (p = .07). CONCLUSION: Image-guided marking is prior to manual marking. As it can bring less toric IOL axis misalignment, less postoperative astigmatism, better postoperative UDVA and smaller difference vector for the patients with toric IOL implantation.

Combined Surgery Versus Phacoemulsification Alone for Patients with Primary Angle­Closure Glaucoma: A meta-analysis.

PURPOSES: The purpose of this meta-analysis is to systematically compare the efficacy and safety between combined surgery (phacoemulsification combined with trabeculectomy) and phacoemulsification for primary angle­closure glaucoma (PACG) patients. METHODS: This work was done through the data searched from the PubMed, EMBASE and the Cochrane Library. The Cochrane Handbook was also used to evaluate the quality of the included studies. In addition, this meta-analysis was performed using Revman 5.4 software. RESULTS: A total of seven randomized controlled trials (RCTs) were included. Compared with phacoemulsification alone, combined surgery resulted in significant reduction in the IOP (MD = -1.45, 95%CI, -2.38 to -0.51, p = .002). And more reduction in number of glaucoma medications was shown in the combined surgery group (MD, -0.59; 95%CI, -1.01 to -0.17; p = .006). For the improvement of the best corrected visual acuity (BCVA), there was no statistical differences between two groups (MD, 0.05; 95%CI, -0.01 to 0.11; p = .08). In subgroup analysis, the BCVA improved more significantly for medically controlled PACG patients in the phacoemulsification alone group (MD, 0.09; 95%CI, 0.01 to 0.07; p = .02). Compared with the phacoemulsification alone group, more complications were shown in the combined surgery group (RR, 0.22; 95%CI, 0.09 to 0.56; p = .001). CONCLUSION: For lowering IOP, combined surgery was superior to phacoemulsification alone for PACG patients. Meanwhile, combined surgery generated more complications. For medically controlled PACG patients, phacoemulsification alone is more conducive to the improvement of BCVA.

Efficacy of intravitreal conbercept injection on short- and long-term macular edema in branch retinal vein occlusion.

AIM: To observe the best-corrected visual acuity (BCVA) and central foveal thickness (CFT) repeatedly after the intravitreal injection of conbercept (IVC) for treating cystoid macular edema (CME) in branch retinal vein occlusion (BRVO) and explore the relationship between the duration of CME and visual outcome. METHODS: Subgroup analysis was performed to compare short-term (within 90d of CME onset) and long-term (over 90d of CME onset) macular edema in BRVO. After an initial IVC, a pro re nata (PRN) strategy was performed according to the recurrence of CFT or decrease of BCVA. Analysis of variance using repeated measurements, statistical analysis following indicators including BCVA and CFT collected at baseline and 1, 3, and 6mo after IVC. RESULTS: Among the 60 cases included in this retrospective study, 36 were short-term CME, and 24 were long-term CME. There were statistical significances between and within groups of the BCVAs at different time points (P<0.001). The interaction was found between group and time (P=0.006), indicating the difference in the speed of BCVA improvement between groups. In particular, the improvement speed of BCVA in the short-term CME group was faster than that in the long-term CME group. There were significant differences between and with groups of the CFT at different time points (P<0.001). However, the interaction between group and time in relation to CFT had no significant differences (P=0.59). CONCLUSION: IVC treatment for CME following BRVO is effective and safe. The duration of CME before treatment is a significant predictor of the visual outcomes of patients with BRVO. The improvement of vision might be faster with early IVC treatment than with delayed treatment.

Dual VEGF/PDGF knockdown suppresses vasculogenic mimicry formation in choroidal melanoma cells via the Wnt5a/ß-catenin/AKT signaling pathway.

OBJECTIVE: This study aimed to explore the effects of knocking down both vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) on vasculogenic mimicry (VM) formation in choroidal melanoma (CM) cells. METHODS: Cell counting Kit (CCK)-8, monoclonal formation, wound healing, transwell and flow cytometry assays were used to observe the cell effects in CM cell line, ocular choroidal melanoma-1 cells (OCM-1) with respect to proliferation, migration, invasion and apoptosis. Three-dimensional (3D) cultures were also used to characterize VM tube structural effects in OCM-1 cells and western blotting was used to characterize protein expression changes in VM-related markers. RESULTS: Dual VEGF/PDGF knockdown suppressed cell proliferation, migration and invasion, but promoted cell apoptosis. It also reduced VM tube structures in OCM-1 cells. VM associated markers including, VE-cadherin, EphA2 and MT1-MMP were also down-regulated in OCM-1 cells. Similarly, Wnt5a, ß-catenin and phosphorylated-AKT levels were also down-regulated. Western blotting and 3D cultures further demonstrated that combined Wnt5a silencing with dual VEGF/PDGF knockdown significantly decreased VE-cadherin and EphA2 levels and reduced VM tube structures in OCM-1 cells. CONCLUSIONS: Dual VEGF/PDGF knockdown suppressed cell growth and metastasis in OCM-1 cells, and blocked the Wnt5a/ß-catenin/AKT signaling pathway thereby inhibiting VM formation.

VEGF Induce Vasculogenic Mimicry of Choroidal Melanoma through the PI3k Signal Pathway.

PURPOSE: To explore the effect of VEGF (vascular endothelial growth factor) on the vasculogenic mimicry (VM) formation of Choroidal Melanoma (CM) through PI3k signal pathway, to find novel targets for CM therapy. METHODS: This research investigated the molecular mechanism of VEGF promoting VM formation of CM. First, we evaluated the expressions of VEGF in 20 CM specimens by immunohistochemical determination. Then we detected expressions of VEGF, AKT, MT1-MMP, MMP2, and MMP9 of OCM-1 in hypoxia. siRNA was used to inhibit the expression of VEGF, to realize the control of the VM formation. The VM formation was evaluated through wound healing assay, transwell assay, and apoptosis. And then we testify the correlation of the VM and the factors in protein and mRNA level preliminarily. RESULTS: VEGF protein was expressed in CM in all 20 cases of CM, especially along the VM. In hypoxia, the expression of VEGF in OCM-1 increased significantly. VEGF gene deletion reduced the proliferation, migration, and invasion of OCM-1. VEGF gene deletion impaired the expression of invasive associated genes like VEGF, p-AKT, AKT, MT1-MMP, MMP2, and MMP9. These results indicate that VEGF induce VM formation in CM by activating PI3K/AKT signaling pathway. CONCLUSIONS: VEGF promoted VM formation by the PI3K signal transduction pathway, indicating a molecular mechanism which may be used to develop new therapeutic targets for the clinical treatment of CM.

Heparinoids Danaparoid and Sulodexide as clinically used drugs.

Heparin is the first glycosaminoglycan ever identified. All the heparin-like glycosaminoglycans that are also isolated from animal tissues or any polysaccharides that mimic the biological activities of heparin are called heparinoids. Heparin is the mostly sulfated glycosaminoglycan made by mast cells and an essential anticoagulant drug in modern medicine. Heparin inhibits both thrombin generation and thrombin activity, releases tissue factor pathway inhibitor, and possesses anti-inflammatory, anti-viral, anti-angiogenesis, anti-neoplastic, and anti-metastatic properties though high affinity interactions with a variety of proteins in the blood circulation. The multi-pharmacological effects of heparin are both sequence- and sulfation degree dependent. Less sulfated heparinoids have been indicated to have more physiological functions than heparin. Since the anticoagulant heparin is associated with severe side effects, such as bleeding and heparin-induced thrombocytopenia and thrombosis, it is expected that the less sulfated heparinoids might serve as alternative drugs for patients who cannot use heparin. The crude heparin isolated from animal tissues contains ~50% heparin and ~50% less sulfated heparinoids. Indeed, the less sulfated waste heparinoids 1 during heparin production is chemically degraded and developed into the clinical drug Danaparoid and the more sulfated waste heparinoids 2 during heparin production is chemically degraded and developed into the clinical drug Sulodexide. Moreover, clinical studies indicate that Danaparoid and Sulodexide have the expected pharmacological activities. We will provide an update on the chemical characteristics and clinical use of the heparinoids Danaparoid and Sulodexide. In addition, the potential clinical applications of Danaparoid and Sulodexide in other therapeutic area will also be discussed.

Function of different proportions of apolipoprotein A-I cysteine mutants and apolipoprotein A-V on recombinant high-density lipoproteins in vitro.

To explore the anti-atherosclerotic effects of recombinant high-density lipoproteins (rHDL) of apolipoprotein AI wild-type (apoA-Iwt), apolipoprotein AI Milano (apoA-IM), apolipoprotein AI (N74C) (apoA-I (N74C) )and apolipoprotein AV (apoA-V). We constructed rHDL liposomes (rHDLs), which included apoA-Iwt, apoA-IM, and apoA-I (N74C), followed by the synthesis of rHDLs, with the indicated ratios of apoA-Iwt, apoA-IM, apoA-I (N74C) and apoA-V. We investigated the anti-atherosclerotic effects by experiments including the DMPC clearance assay and experiments that assessed the in vitro antioxidation against low-density lipoprotein, the cellular uptake of oxidized low-density lipoprotein (oxLDL) and the in vitro intracellular lipid accumulation. Electron microscopy results revealed that as more apoA-V was present in rHDLs, the particle size of rHDLs was larger. The DMPC clearance assay subsequently showed that rHDL protein mixtures could promote DMPC turbidity clearance when more apoA-V was included in the reaction mixtures, with apoAV-rHDL showing the strongest turbidity clearance ability (P<0.05 vs AI-rHDL). In vitro antioxidation against low-density lipoprotein assays indicated that rHDLs containing apoA-V had increasing oxidation resistance against low-density lipoprotein (LDL) with higher apoA-V contents. Finally, cellular uptake of oxLDL and intracellular lipids suggested an apparent oxidation resistance to LDL oxidation in vitro and a reduced intracellular lipid accumulation in THP-1-derived macrophages, with AIM-rHDL demonstrating the greatest ability to decrease intracellular lipid accumulation. Different proportions of apolipoprotein A-I cysteine mutants and apolipoprotein A-V of rHDL changed the lipid binding capacity, particle size, and antioxidant capacity. These changes may show a beneficial effect of rHDL on atherosclerosis.

Effect of lipid-bound apolipoprotein A-I cysteine mutant on ATF3 in RAW264.7 cells.

Activating transcription factor 3 (ATF3) is a TLR-induced repressor that plays an important role in the inhibition of specific inflammatory signals. We previously constructed recombinant high density lipoproteins (rHDL) (including rHDLWT, rHDLM, rHDL228 and rHDL74) and found that rHDL74 had a strong anti-inflammatory ability. In the present study, we investigate the roles of recombinant apolipoprotein A-I (ApoA-I) (rHDLWT) and its cysteine mutant HDLs (rHDLM, rHDL228 and rHDL74) on ATF3 function in RAW264.7 cells stimulated by lipopolysaccharide. Our results showed that compared with the LPS group, rHDL74 can decrease the level of TNF-α and IL-6, whereas rHDL228 increases their expression levels. RT-PCR and Western blotting results showed that compared with the LPS group, rHDL74, rHDLWT and rHDLM can markedly increase the expression level of ATF3, whereas the level of ATF3 decreases in the rHDL228 group. In summary, the different anti-inflammatory mechanisms of the ApoA-I cysteine mutants might be associated with the regulation of ATF3 level.