RNA activating-double stranded RNA targeting flt-1 promoter inhibits endothelial cell proliferation through soluble FLT-1 upregulation.

Short-activating RNA (saRNA), which targets gene promoters, has been shown to increase the target gene expression. In this study, we describe the use of an saRNA (Flt a-1) to target the flt-1 promoter, leading to upregulation of the soluble isoform of Flt-1 and inhibition of angiogenesis. We demonstrate that Flt a-1 increased sFlt-1 mRNA and protein levels, while reducing VEGF expression. This was associated with suppression of human umbilical vascular endothelial cell (HUVEC) proliferation and cell cycle arrest at the G0/G1 phase. HUVEC migration and tube formation were also suppressed by Flt a-1. An siRNA targeting Flt-1 blocked the effects of Flt a-1. Flt a-1 effects were not mediated via argonaute proteins. However, trichostatin A and 5'-deoxy-5'-(methylthio) adenosine inhibited Flt a-1 effects, indicating that histone acetylation and methylation are mechanistically involved in RNA activation of Flt-1. In conclusion, RNA activation of sFlt-1 can be used to inhibit angiogenesis.

Comparative analysis of the safety and efficacy of intracameral cefuroxime, moxifloxacin and vancomycin at the end of cataract surgery: a meta-analysis.

BACKGROUND: Current practice methods are unclear as to the most safe and effective prophylactic pharmacotherapy and method of delivery to reduce postoperative endophthalmitis occurrence. METHODS: A systematic review and meta-analysis using Meta-analysis of Observational Studies in Epidemiology guidelines was performed to compare the efficacy of intracameral cefuroxime, moxifloxacin and vancomycin in preventing postphacoemulsification cataract surgery endophthalmitis. A safety analysis of intracameral antibiotics was concurrently performed. DATA SOURCES: BIOSIS Previews, CINAHL, ClinicalTrials.gov, Cochrane Library, Dissertations & Theses, EMBASE, PubMed, ScienceDirect and Scopus were searched from inception to January 2017. Data were pooled using a random effects model. All articles were individually reviewed and data were extracted by two independent reviewers. Funnel plot, risk of bias and quality of evidence analyses were performed. RESULTS: Seventeen studies with over 900 000 eyes were included, which favoured the use of intracameral antibiotics at the end of cataract surgery (OR 0.20; 95% CI 0.13 to 0.32; P<0.00001). The average weighted postoperative endophthalmitis incidence rates with intracameral cefuroxime, moxifloxacin and vancomycin were 0.0332%, 0.0153% and 0.0106%, respectively. Secondary analyses showed no difference in efficacy between intracameral plus topical antibiotics versus intracameral alone (P>0.3). Most studies had low to moderate risk of bias. The safety analysis showed minimal toxicity for moxifloxacin. Dosing errors led to the majority of toxicities with cefuroxime. Although rare, vancomycin was associated with toxic retinal events. CONCLUSION: Intracameral cefuroxime and moxifloxacin reduced endophthalmitis rates compared with controls with minimal or no toxicity events at standard doses. Additionally, intracameral antibiotics alone may be as effective as intracameral plus topical antibiotics.

Sutureless Lamellar Corneoscleral Patch Graft With Fibrin Sealant for Limbal Dermoid Removal.

A 2-year-old boy with Goldenhar syndrome had a limbal dermoid removed and covered with a lamellar corneoscleral patch graft that was attached with fibrin glue and no sutures. The graft healed and attached well. A sutureless technique is beneficial due to decreased scarring and chance of infection.

Safety of undiluted intracameral moxifloxacin without postoperative topical antibiotics in cataract surgery.

The objective of this study is to evaluate the safety of undiluted 0.5 % intracameral moxifloxacin for postoperative endophthalmitis prophylaxis in cataract surgery patients without the use of additional postoperative topical antibiotics. All phacoemulsification cataract surgeries performed by a single surgeon (B.A.) at the John A. Moran Eye Center from June 2012 to May 2015 were reviewed retrospectively. From June 2012 to April 2014, patients were given topical 0.5 % moxifloxacin postoperatively. From May 2014 to May 2015, all patients were given moxifloxacin intracamerally with no antibiotics postoperatively. The follow-up period was 1 month after surgery. Preoperative visual acuity and postoperative visual acuity, corneal edema, and anterior chamber reaction were recorded and compared between the two groups. 384 cataract surgeries were performed during the study period. None of the 384 eyes in the study developed endophthalmitis. Of those 384 eyes, 222 were included in the study for analysis based on the inclusion and exclusion criteria. 131 were part of the topical antibiotic group and 91 were part of the intracameral group. The differences in uncorrected visual acuity at 1 day postoperatively (p = 0.595) and best corrected visual acuity at 1 month postoperatively (p = 0.099) were not statistically significant. Differences in corneal edema (p = 0.370) and anterior chamber reaction (p = 0.069) at 1 day postoperatively and corneal edema (p = 0.512) and anterior chamber reaction (p = 0.512) at 1 month postoperatively were also not statistically significant. Undiluted 0.5 % moxifloxacin can be safely injected intracamerally following cataract surgery without additional postoperative antibiotic prophylaxis to prevent endophthalmitis without adverse effects on patient outcomes.