Characteristics of multi-mode lasing in cesium lead bromide perovskite microwires with an isosceles right triangle cross-section.

The CsPbBr3 microwires with unique isosceles right triangle cross-sections are commonly observed via chemical vapor deposition method. In this work, we study the correlations between measured multi-mode lasing behaviors and the simulation of the mode patterns inside the triangular-rod microcavity. We confirm that lasing action with higher-order transverse modes can well sustain, even when these modes experience large optical loss due to the isosceles triangle cross-section. By comparing the experimental and simulation results, the higher-order transverse modes tend to show up prior to the fundamental transverse modes for wider microwires. We attribute this behavior to the nonuniform field distribution caused by the high absorption efficiency of CsPbBr3. We also elaborate on the difficulties to sustain the whispering gallery mode in the CsPbBr3 triangular-rod microcavity, which implies that the lateral dimension and geometry of the cavity should be considered carefully for the future design of low threshold wire-based laser devices.

Glycyrrhetinic acid derivatives as Zika virus inhibitors: Synthesis and antiviral activity in vitro.

Zika virus (ZIKV) is an arbovirus of the Flaviviridae family (Flavivirus genus), causing serious neurological complications, such as Guillain-Barre Syndrome (GBS) in adults and fetal microcephaly. Licensed vaccines or specific antiviral agents against ZIKV do not currently exist. Therefore, the search and development of anti-ZIKV agents are particularly relevant and necessary. Glycyrrhetinic (3ß-hydroxy-11-oxo-18ßH-Olean-12-en-30-oic acid) (GA) 1 is one of the well-known pentacyclic triterpenoids isolated from licorice root (Glycyrrhiza glabra L., Gl. uralensis Fisher) (Leguminosae) possessing many biological features, including antiviral activity. This paper is devoted to the synthesis and studies of a number of nitrogen and sulfur-containing GA derivatives as ZIKV inhibitors. Sixteen GA and related triterpenoids (3ß-hydroxy-18ßH-Olean-12-en-30-oic acid and 3ß-hydroxy-11-oxo-18ßH-Olean-12(13),18(19)-dien-30-oic acid) derivatives were synthesized (amides, semi- and thiosemicarbazones, and 1,2,3-thiadiazoles) and antiviral activity against ZIKV was studied in vitro, including the inhibitory assays on cytopathic effect (CPE), viral protein synthesis, and replication stages. Four active compounds were found among GA derivatives tested, 13 (3-O-acetyl-30-aminopyridine GA), 16 (3-semicarbazone-30-butyl GA), 18 (1,2,3-thiadiazole-30-methyl GA), and 19 (1,2,3-thiadiazole-30-butyl GA) with IC50 < 1 µM against ZIKV replication. These compounds had a stronger inhibitory activity on ZIKV-induced CPE and viral protein translation in infected cells as compared to derivatives of 11-desoxo-GA. The most active compound was amide 13 (IC50 0.13 µM, TI ˃ 384). Time-of-addition assays indicated that 1,2,3-thiadiazole ring is important for inhibiting viral entry stage (compounds 18 and 19), while the 30-butyl ester group influenced on post-entry stage (compound 19). The molecular docking analysis demonstrated that lead compounds 13 and 19 forms a hydrogen-bond interaction with the catalytic triad (His51-Asp75-Ser135) of ZIKV NS2B-NS3 protease. Therefore, the active GA derivatives are promising for developing new antiviral agents against ZIKV infection.

Antiviral activity of glycyrrhizic acid conjugates with amino acid esters against Zika virus.

Zika virus (ZIKV) is a new pathogenic flavivirus transmitted by mosquitoes Aedes spp. ZIKV infection is accompanied by serious neurological complications and is especially dangerous for pregnant women, in which it can lead to congenital malformations of the fetus and microcephaly in neonates. Currently, there are no licensed vaccines or specific post-infectious therapies for ZIKV infection. This report is devoted to the study of glycyrrhizic acid (GL) derivatives as ZIKV inhibitors. The inhibitory assays on the cytopathic effect (CPE) and viral infectivity of ZIKV in three different human cell lines revealed that the conjugation of GL with amino acids and their esters (methyl, ethyl) is influenced by the antiviral activity of the compounds. GL conjugates with Glu(OMe)-OMe 11, Glu(OH)-OMe 12, Asp(OMe)-OMe 13, TyrOMe 14, LeuOEt 15, and PheOEt 16 with free COOH groups in the triterpene moiety were active against ZIKV. The most active compounds 13 and 14 have IC50 values of 0.23 µM and 0.09 µM against low doses (MOI = 0.05) of ZIKV strain PRVABC59, 1.20 µM and 0.74 µM against high doses (MOI = 10) of ZIKV strain Natal RGN single-round infectious particles, respectively. The lead compound was 14 with a high selectivity index (SI < 500). Compound 13 showed a higher inhibitory effect on the early stage (entry) of ZIKV replication than compound 14, and was less potent than compound 14 at the post-entry stage, consistent with the docking models. Compounds 13 and 14 also had a strong interaction with the active site pocket of NS5 MTase. Compounds 13 and 14 are recommended for expanded antiviral studies against ZIKV infection.

Combined delivery of sorafenib and a MEK inhibitor using CXCR4-targeted nanoparticles reduces hepatic fibrosis and prevents tumor development.

Liver damage and fibrosis are precursors of hepatocellular carcinoma (HCC). In HCC patients, sorafenib-a multikinase inhibitor drug-has been reported to exert anti-fibrotic activity. However, incomplete inhibition of RAF activity by sorafenib may also induce paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway in malignant cells. The consequence of this effect in non-malignant disease (hepatic fibrosis) remains unknown. This study aimed to examine the effects of sorafenib on activated hepatic stellate cells (HSCs), and develop effective therapeutic approaches to treat liver fibrosis and prevent cancer development. Methods: We first examined the effects of sorafenib in combination with MEK inhibitors on fibrosis pathogenesis in vitro and in vivo. To improve the bioavailability and absorption by activated HSCs, we developed CXCR4-targeted nanoparticles (NPs) to co-deliver sorafenib and a MEK inhibitor to mice with liver damage. Results: We found that sorafenib induced MAPK activation in HSCs, and promoted their myofibroblast differentiation. Combining sorafenib with a MEK inhibitor suppressed both paradoxical MAPK activation and HSC activation in vitro, and alleviated liver fibrosis in a CCl4-induced murine model of liver damage. Furthermore, treatment with sorafenib/MEK inhibitor-loaded CXCR4-targeted NPs significantly suppressed hepatic fibrosis progression and further prevented fibrosis-associated HCC development and liver metastasis. Conclusions: Our results show that combined delivery of sorafenib and a MEK inhibitor via CXCR4-targeted NPs can prevent activation of ERK in activated HSCs and has anti-fibrotic effects in the CCl4-induced murine model. Targeting HSCs represents a promising strategy to prevent the development and progression of fibrosis-associated HCC.

Overcoming sorafenib evasion in hepatocellular carcinoma using CXCR4-targeted nanoparticles to co-deliver MEK-inhibitors.

Sorafenib is a RAF inhibitor approved for several cancers, including hepatocellular carcinoma (HCC). Inhibition of RAF kinases can induce a dose-dependent "paradoxical" upregulation of the downstream mitogen-activated protein kinase (MAPK) pathway in cancer cells. It is unknown whether "paradoxical" ERK activation occurs after sorafenib therapy in HCC, and if so, if it impacts the therapeutic efficacy. Here, we demonstrate that RAF inhibition by sorafenib rapidly leads to RAF dimerization and ERK activation in HCCs, which contributes to treatment evasion. The transactivation of RAF dimers and ERK signaling promotes HCC cell survival, prevents apoptosis via downregulation of BIM and achieves immunosuppression by MAPK/NF-kB-dependent activation of PD-L1 gene expression. To overcome treatment evasion and reduce systemic effects, we developed CXCR4-targeted nanoparticles to co-deliver sorafenib with the MEK inhibitor AZD6244 in HCC. Using this approach, we preferentially and efficiently inactivated RAF/ERK, upregulated BIM and down-regulated PD-L1 expression in HCC, and facilitated intra-tumoral infiltration of cytotoxic CD8+ T cells. These effects resulted in a profound delay in tumor growth. Thus, this nano-delivery strategy to selectively target tumors and prevent the paradoxical ERK activation could increase the feasibility of dual RAF/MEK inhibition to overcome sorafenib treatment escape in HCC.

Dual-Functional Nanoparticles Targeting CXCR4 and Delivering Antiangiogenic siRNA Ameliorate Liver Fibrosis.

The progression of liver fibrosis, an intrinsic response to chronic liver injury, is associated with hepatic hypoxia, angiogenesis, abnormal inflammation, and significant matrix deposition, leading to the development of cirrhosis and hepatocellular carcinoma (HCC). Due to the complex pathogenesis of liver fibrosis, antifibrotic drug development has faced the challenge of efficiently and specifically targeting multiple pathogenic mechanisms. Therefore, CXCR4-targeted nanoparticles (NPs) were formulated to deliver siRNAs against vascular endothelial growth factor (VEGF) into fibrotic livers to block angiogenesis during the progression of liver fibrosis. AMD3100, a CXCR4 antagonist that was incorporated into the NPs, served dual functions: it acted as a targeting moiety and suppressed the progression of fibrosis by inhibiting the proliferation and activation of hepatic stellate cells (HSCs). We demonstrated that CXCR4-targeted NPs could deliver VEGF siRNAs to fibrotic livers, decrease VEGF expression, suppress angiogenesis and normalize the distorted vessels in the fibrotic livers in the carbon tetrachloride (CCl4) induced mouse model. Moreover, blocking SDF-1α/CXCR4 by CXCR4-targeted NPs in combination with VEGF siRNA significantly prevented the progression of liver fibrosis in CCl4-treated mice. In conclusion, the multifunctional CXCR4-targeted NPs delivering VEGF siRNAs provide an effective antifibrotic therapeutic strategy.

Development and characterization of sorafenib-loaded PLGA nanoparticles for the systemic treatment of liver fibrosis.

Sorafenib is a tyrosine kinase inhibitor that has recently been shown to be a potential antifibrotic agent. However, a narrow therapeutic window limits the clinical use and therapeutic efficacy of sorafenib. Herein, we have developed and optimized nanoparticle (NP) formulations prepared from a mixture of poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (PEG-PLGA) copolymers with poly(lactic-co-glycolic acid) (PLGA) for the systemic delivery of sorafenib into the fibrotic livers of CCl4-induced fibrosis mouse models. We characterized and compared the pharmaceutical and biological properties of two different PLGA nanoparticles (NPs)--PEG-PLGA NPs (PEG-PLGA/PLGA=10/0) and PEG-PLGA/PLGA NPs (PEG-PLGA/PLGA=5/5). Increasing the PLGA content in the PEG-PLGA/PLGA mixture led to increases in the particle size and drug encapsulation efficacy and a decrease in the drug release rate. Both PEG-PLGA and PEG-PLGA/PLGA NPs significantly prolonged the blood circulation of the cargo and increased the uptake by the fibrotic livers. The systemic administration of PEG-PLGA or PEG-PLGA/PLGA NPs containing sorafenib twice per week for a period of 4 weeks efficiently ameliorated liver fibrosis, as indicated by decreased α-smooth muscle actin (α-SMA) content and collagen production in the livers of CCl4-treated mice. Furthermore, sorafenib-loaded PLGA NPs significantly shrank the abnormal blood vessels and decreased microvascular density (MVD), leading to vessel normalization in the fibrotic livers. In conclusion, our results reflect the clinical potential of sorafenib-loaded PLGA NPs for the prevention and treatment of liver fibrosis.

CXCR4-targeted lipid-coated PLGA nanoparticles deliver sorafenib and overcome acquired drug resistance in liver cancer.

Sorafenib, a multikinase inhibitor, has been used as an anti-angiogenic agent against highly vascular hepatocellular carcinoma (HCC) - yet associated with only moderate therapeutic effect and the high incidence of HCC recurrence. We have shown intratumoral hypoxia induced by sorafenib activated C-X-C receptor type 4 (CXCR4)/stromal-derived factor 1α (SDF1α) axis, resulting in polarization toward a tumor-promoting microenvironment and resistance to anti-angiogenic therapy in HCC. Herein, we formulated sorafenib in CXCR4-targeted lipid-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) modified with a CXCR4 antagonist, AMD3100 to systemically deliver sorafenib into HCC and sensitize HCC to sorafenib treatment. We demonstrated that CXCR4-targeted NPs efficiently delivered sorafenib into HCCs and human umbilical vein endothelial cells (HUVECs) to achieve cytotoxicity and anti-angiogenic effect in vitro and in vivo. Despite the increased expression of SDF1α upon the persistent hypoxia induced by sorafenib-loaded CXCR4-targeted NPs, AMD3100 attached to the NPs can block CXCR4/SDF1α, leading to the reduced infiltration of tumor-associated macrophages, enhanced anti-angiogenic effect, a delay in tumor progression and increased overall survival in the orthotopic HCC model compared with other control groups. In conclusion, our results highlight the clinical potential of CXCR4-targeted NPs for delivering sorafenib and overcoming acquired drug resistance in liver cancer.

Ectopic expression of nolz-1 in neural progenitors promotes cell cycle exit/premature neuronal differentiation accompanying with abnormal apoptosis in the developing mouse telencephalon.

Nolz-1, as a murine member of the NET zinc-finger protein family, is expressed in post-mitotic differentiating neurons of striatum during development. To explore the function of Nolz-1 in regulating the neurogenesis of forebrain, we studied the effects of ectopic expression of Nolz-1 in neural progenitors. We generated the Cre-loxP dependent conditional transgenic mice in which Nolz-1 was ectopically expressed in proliferative neural progenitors. Ectopic expression of Nolz-1 in neural progenitors by intercrossing the Nolz-1 conditional transgenic mice with the nestin-Cre mice resulted in hypoplasia of telencephalon in double transgenic mice. Decreased proliferation of neural progenitor cells were found in the telencephalon, as evidenced by the reduction of BrdU-, Ki67- and phospho-histone 3-positive cells in E11.5-12.5 germinal zone of telencephalon. Transgenic Nolz-1 also promoted cell cycle exit and as a consequence might facilitate premature differentiation of progenitors, because TuJ1-positive neurons were ectopically found in the ventricular zone and there was a general increase of TuJ1 immunoreactivity in the telencephalon. Moreover, clusters of strong TuJ1-expressing neurons were present in E12.5 germinal zone. Some of these strong TuJ1-positive clusters, however, contained apoptotic condensed DNA, suggesting that inappropriate premature differentiation may lead to abnormal apoptosis in some progenitor cells. Consistent with the transgenic mouse analysis in vivo, similar effects of Nozl-1 over-expression in induction of apoptosis, inhibition of cell proliferation and promotion of neuronal differentiation were also observed in three different N18, ST14A and N2A neural cell lines in vitro. Taken together, our study indicates that ectopic expression of Nolz-1 in neural progenitors promotes cell cycle exit/premature neuronal differentiation and induces abnormal apoptosis in the developing telencephalon.

Identification of two evolutionarily conserved 5' cis-elements involved in regulating spatiotemporal expression of Nolz-1 during mouse embryogenesis.

Proper development of vertebrate embryos depends not only on the crucial funtions of key evolutionarily conserved transcriptional regulators, but also on the precisely spatiotemporal expression of these transcriptional regulators. The mouse Nolz-1/Znf503/Zfp503 gene is a mammalian member of the conserved zinc-finger containing NET family. The expression pattern of Nolz-1 in mouse embryos is highly correlated with that of its homologues in different species. To study the spatiotemporal regulation of Nolz-1, we first identified two evolutionarily conserved cis-elements, UREA and UREB, in 5' upstream regions of mouse Nolz-1 locus. We then generated UREA-LacZ and UREB-LacZ transgenic reporter mice to characterize the putative enhancer activity of UREA and UREB. The results indicated that both UREA and UREB contained tissue-specific enhancer activity for directing LacZ expression in selective tissue organs during mouse embryogensis. UREA directed LacZ expression preferentially in selective regions of developing central nervous system, including the forebrain, hindbrain and spinal cord, whereas UREB directed LacZ expression mainly in other developing tissue organs such as the Nolz-1 expressing branchial arches and its derivatives, the apical ectodermal ridge of limb buds and the urogenital tissues. Both UREA and UREB directed strong LacZ expression in the lateral plate mesoderm where endogenous Nolz-1 was also expressed. Despite that the LacZ expression pattern did not full recapitulated the endogenous Nolz-1 expression and some mismatched expression patterns were observed, co-expression of LacZ and Nolz-1 did occur in many cells of selective tissue organs, such as in the ventrolateral cortex and ventral spinal cord of UREA-LacZ embryos, and the urogenital tubes of UREB-LacZ embryos. Taken together, our study suggests that UREA and UREB may function as evolutionarily conserved cis-regulatory elements that coordinate with other cis-elements to regulate spatiotemporal expression of Nolz-1 in different tissue organs during mouse embryogenesis.

Region- and cell type-selective expression of the evolutionarily conserved Nolz-1/zfp503 gene in the developing mouse hindbrain.

Nolz-1/Zfp503, a zinc finger-containing gene, is a mammalian member of the SP1-related nocA/elb/tlp-1 gene family. Previous studies have shown that Nolz-1 homologs are important for patterning the rhombomeres in zebrafish hindbrain. We therefore studied the expression pattern of Nolz-1 in the developing mouse hindbrain. Nolz-1 mRNA expression was detected in the prospective rhombomere 3, 5 and caudal regions as early as E8.75. After E11.5, Nolz-1-positive cells were organized as distinct cell clusters, and they were largely non-overlapped with either Pax2-positive or Phox2b-positive domains. Most interestingly, we found that Nolz-1 was specifically expressed by Phox2b-negative/Isl1/2-positive somatic motor neurons, but not by Phox2b-positive/Isl1/2-positive branchial and visceral motor neurons, suggesting that Nolz-1 may regulate development of somatic motor neurons in the hindbrain. In addition to be expressed in differentiating post-mitotic neurons, Nolz-1 was also expressed by progenitor cells in the ventricular zone located in the dorsal part of aqueduct and the alar plates of hindbrain, which suggests a regulatory role of Nolz-1 in the germinal zone. Taken together, based on its domain- and cell type-selective pattern, Nolz-1 may involve in regulation of various developmental processes, including regional patterning and cell-type specification and differentiation in the developing mouse hindbrain.

Intravitreal injection of 2.5 mg bevacizumab for treatment of myopic choroidal neovascularization in treatment-naive cases: a 2-year follow-up.

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of intravitreal bevacizumab in treatment-naive patients with choroidal neovascularization (CNV) secondary to pathologic myopia over a 2-year interval. METHODS: Patients diagnosed with myopic CNV who had not received previous treatment were given intravitreal injections of bevacizumab (2.5 mg/0.1 mL). All patients were retrospectively evaluated using best-corrected visual acuity (BCVA) and central macular thickness (CMT) measured with optical coherence tomography (OCT). RESULTS: Twenty-six eyes of 26 patients aged 15-81 years (mean, 42.6 years) were enrolled. OCT images demonstrated that the mean CMT±standard deviation (SD) significantly changed from 270±47 µm at baseline to 228±35, 218±35, 212±25, 210±29, and 209±30 µm in the 1st, 3rd, 6th, 12th, and 24th post-treatment months, respectively (P<0.001 for all). The BCVA in logarithm of the minimum angle of resolution±SD significantly changed from 0.75±0.43 at baseline to 0.57±0.44, 0.42±0.44, 0.39±0.47, 0.41±0.44, and 0.42±0.41 in the 1st, 3rd, 6th, 12th, and 24th post-treatment months, respectively (P<0.001 for all). The mean number of injections was 1.69 (range, 1-4) within the 24-month period. The follow-up period ranged from 24 to 35 months (mean, 28 months). No other ocular or systemic adverse effects were observed. CONCLUSIONS: Although the present study lacked a control group, the results in this small series of patients over the 2-year follow-up period indicate that intravitreal injection of 2.5 mg bevacizumab is effective and safe in patients with myopic CNV.

Intravitreal bevacizumab injection therapy for persistent macular edema after idiopathic macular epiretinal membrane surgery.

PURPOSE: The purpose of this study was to evaluate the effects of intravitreal bevacizumab (ivBe) injection in patients with persistent macular edema after macular epiretinal membrane (ERM) removal. METHODS: This retrospective study included 26 patients (26 eyes) with marked macular edema after complete removal of idiopathic macular ERM who received single ivBe injection (12 patients) or no treatment (controls, 14 patients). Main outcome measurements were central macular thickness (CMT) and best-corrected visual acuity (BCVA). RESULTS: In the ivBe group, the mean CMT±standard deviation (SD) changed significantly from 323±43 µm at baseline to 306±41, 301±42, and 296±41 µm at weeks 4, 8, and 12, respectively, after treatment (P= 0.025, <0.0001, and <0.0001, respectively). The BCVA in logarithm of the minimum angle of resolution (logMAR)±SD did not change significantly from 0.50±0.15 at baseline to 0.46±0.11, 0.44±0.14, 0.44±0.14, and 0.42±0.13 at weeks 1, 4, 8, and 12, respectively, after treatment (P>0.05 for all). In the control group, the mean CMT±SD changed significantly from 326±32 µm at baseline to 314±29, 308±29, and 307±30 µm at weeks 4, 8, and 12, respectively, after treatment (P=0.002, <0.0001, and <0.0001, respectively). The BCVA in logMAR±SD did not change significantly from 0.52±0.22 at baseline to 0.49±0.20, 0.47±0.22, 0.45±0.16, and 0.47±0.23 at modified weeks 1, 4, 8, and 12, respectively, after treatment (P>0.05 for all). No significant differences were found for CMT or BCVA between the ivBe group and the control group at baseline and at any checkpoints after treatment (P>0.05 for all). CONCLUSION: ivBe injection therapy provided no beneficial effects on CMT or visual acuity improvement for eyes with persistent macular edema after idiopathic macular ERM removal.

Treatment of branch retinal vein occlusion induced macular edema in treatment-naïve cases with a single intravitreal triamcinolone or bevacizumab injection.

BACKGROUND: To evaluate the effects of a single intravitreal injection of triamcinolone acetonide (ivTA) or bevacizumab (ivBe) on visual acuity and central macular thickness (CMT) in cases of macular edema secondary to branch retinal vein occlusion (BRVO) for eyes that are treatment-naïve. METHODS: This consecutive, retrospective, nonrandomized, clinical interventional study included 83 patients (83 eyes) with macular edema secondary to BRVO who received single ivTA (25 patients) or ivBe (24 patients) injections, or no treatment (controls, 34). The main outcomes included CMT measurements using optical coherence tomography (OCT) and best-corrected visual acuity (BCVA). RESULTS: CMT decreased significantly from baseline at 4, 8, 12 and 24 weeks after treatment (p < 0.05) in both the intravitreal groups and the control group. BCVA improved significantly from baseline at 4 and 8 weeks after treatment among the ivTA group (p < 0.05) and at 4, 8 and 12 weeks after treatment among the ivBe group (p < 0.05). Comparing CMT between the groups, significant differences were found between ivTA and control groups and ivBe and control groups at the 4- and 8- week checkpoints (p < 0.05). Significant differences were found in BCVA only between ivBe and control groups at the 8-week checkpoint (p = 0.049). No significant differences were found for CMT and BCVA between the ivBe and ivTA groups (p > 0.05) at any checkpoint after treatment. No patient experienced immediate procedure-related complications or any obvious systemic adverse events in either the ivTA group or the ivBe group. Delayed complications included steroid induced ocular hypertension in eight eyes (32%) and development of posterior subcapsular cataracts in five eyes (28%) in the ivTA group. CONCLUSIONS: Both the ivTA and ivBe therapies were beneficial short-term treatment options for the treatment of macular edema secondary to BRVO. However, the ivBe treatment appears to be safer and less prone to adverse side effects such as ocular hypertension and cataract compared with ivTA therapy.

Adjunctive intravitreal bevacizumab-combined trabeculectomy versus trabeculectomy alone in the treatment of neovascular glaucoma.

PURPOSE: To evaluate the effect of adjunctive intravitreal bevacizumab (ivBe) with trabeculectomy versus trabeculectomy alone in the management of patients with neovascular glaucoma (NVG). METHODS: Retrospective, consecutive, interventional case series. NVG patients were divided into groups by treatment: with adjunctive ivBe and trabeculectomy (ivBe group, n = 14 eyes) and with trabeculectomy only (control group, n = 28 eyes). The main outcome measure was visual acuity. Regression of iris neovascularization (NVI), change(s) in intraocular pressure (IOP), NVI recurrence, additional glaucoma surgeries required, eyes of leading to total blindness, intraoperative and postoperative complications, and number of topical medications required after trabeculectomy were regarded as second outcome measures. In the ivBe group, intravitreal injections of 2.5 mg bevacizumab were delivered using a sharp 27-gauge needle through the inferotemporal quadrant. RESULTS: Of 42 eyes of 42 patients identified, change in IOP, additional glaucoma surgeries required, and number of IOP-lowering topical medications required after trabeculectomy did not differ significantly between groups (P > 0.05 for all). However, the ivBe group had significantly higher frequency and rapidity of iris neovascular regression, improved visual acuity in the logarithm of minimum angle of resolution (logMAR), leading to total blindness in fewer eyes and intraoperative and postoperative complications in others than in the control group (P = 0.015, 0.002, 0.007, 0.023, and 0.008, respectively). The follow-up duration (mean +/- SD) from trabeculectomy surgery was 179 +/- 97 days (range, 93-315 days) and 196 +/- 108 days (range, 92-370 days) in the ivBe and control group (P = 0.324). CONCLUSIONS: Intravitreal bevacizumab might be a useful adjunctive therapy in addition to trabeculectomy in the management of NVG. Large controlled randomized studies for treatment of bevacizumab on NVG are warranted.

The combination of intravitreal bevacizumab and phacoemulsification surgery in patients with cataract and coexisting diabetic macular edema.

PURPOSE: The aim of this study was to assess the efficacy of phacoemulsification combined with intravitreal (i.v.t.) bevacizumab injection in diabetics with clinically significant macular edema (CSME) and cataract. METHODS: This retrospective study included diabetic patients with cataract and CSME who underwent phacoemulsification and intraocular lens implantation with a 2.5-mg bevacizumab i.v.t injection (ivBe) (15 eyes) or without ivBe (controls, 14 eyes). Best-corrected visual acuity (BCVA), central macular thickness (CMT) measured by optic coherence tomography (OCT), and adverse events were recorded. RESULTS: In the ivBe group, the OCT images demonstrated that CMT (mean +/- standard deviation [SD]) decreased significantly from 466 +/- 105 at baseline to 333 +/- 107, 313 +/- 138 and 333 +/- 111 microm at 4, 8, and 12 weeks, respectively, after treatment (P < 0.05). The visual acuity in logMAR (mean +/- SD) improved significantly from 1.66 +/- 0.39 at baseline to 1.30 +/- 0.50, 1.15 +/- 0.42, 0.99 +/- 0.48, and 1.03+/- 0.44 at 1, 4, 8, and 12 weeks, respectively, after treatment (P < 0.05). However, in the control group, the CMT changed insignificantly from 443 +/- 109 at baseline to 463 +/- 106, 425 +/- 128, and 421 +/- 119 microm at 4, 8 and 12 weeks, respectively after treatment (P > 0.05). The visual acuity in logMAR improved insignificantly from 1.63 +/- 0.42 at baseline to 1.43 +/- 0.53, and 1.39 +/- 0.43 at 1, and 4 weeks (P > 0.05) and significantly to 1.24 +/- 0.45 and 1.18 +/- 0.44 at 8 and 12 weeks, respectively, after treatment (P < 0.05). None of the patients in both groups experienced injection- or surgery-related complications or any obvious systemic adverse events. CONCLUSIONS: The short-term results suggest that phacoemulsification with i.v.t. bevacizumab safely reduces macular edema and improves visual acuity for cataract and CSME in diabetics.