Biocompatible, Purified VEGF-A mRNA Improves Cardiac Function after Intracardiac Injection 1 Week Post-myocardial Infarction in Swine.

mRNA can direct dose-dependent protein expression in cardiac muscle without genome integration, but to date has not been shown to improve cardiac function in a safe, clinically applicable way. Herein, we report that a purified and optimized mRNA in a biocompatible citrate-saline formulation is tissue specific, long acting, and does not stimulate an immune response. In small- and large-animal, permanent occlusion myocardial infarction models, VEGF-A 165 mRNA improves systolic ventricular function and limits myocardial damage. Following a single administration a week post-infarction in mini pigs, left ventricular ejection fraction, inotropy, and ventricular compliance improved, border zone arteriolar and capillary density increased, and myocardial fibrosis decreased at 2 months post-treatment. Purified VEGF-A mRNA establishes the feasibility of improving cardiac function in the sub-acute therapeutic window and may represent a new class of therapies for ischemic injury.

Long-Term Outcome of Intravitreal Bevacizumab Followed by Ahmed Valve Implantation in the Management of Neovascular Glaucoma.

BACKGROUND: To report the outcome of intravitreal Bevacizumab followed by Ahmed valve implantation in the management of neovascular glaucoma in a patient group with extended follow-up. METHODS: The records of 16 patients (18 eyes) with neovascular glaucoma refractory to medical therapy who presented to a single surgeon between 2006-2008 were reviewed. Patients received pan-retinal photocoagulation and then intravitreal Bevacizumab followed by Ahmed valve implantation. The main outcome measures were: control of IOP (with or without additional medication), visual acuity (VA) and failure (IOP >21 mmHg or <6 mmHg, reoperation for glaucoma, or loss of light perception). RESULTS: Pre-operatively, all patients received pan-retinal photocoagulation followed by IVB at a mean of 15.9 (range 4-60) days prior to AGV. The mean pre-operative IOP was 37.1 mmHg (±13.4) on 3.2 (±0.87) medications. Of the 18 eyes, 14 eyes (78%) were treated with AGV alone and 4 eyes (22%) with AGV combined with cataract extraction. Sixteen eyes (89%) received mitomycin C treatment intraoperatively. Post-operatively, the mean follow-up period was 63 months (24-84). At final follow-up, the success rate was 50% (33.3% complete, 16.7% qualified) with a mean IOP of 18.1 mmHg (±9.5) on a mean number of 1.5 (±1.6) medications. The failure rate was 50%, with five eyes (27.8%) not meeting the IOP criteria for success (of these, three eyes required additional surgery to lower the IOP) and five eyes (22.2%) lost light perception. CONCLUSION: Intravitreal Bevacizumab followed by AGV offers long-term control of IOP without additional surgical intervention in the majority of cases.

Mitomycin C versus 5-Fluorouracil for wound healing in glaucoma surgery.

BACKGROUND: Raised intraocular pressure is a risk factor for glaucoma. One treatment option is glaucoma drainage surgery (trabeculectomy). Antimetabolites are used during surgery to reduce postoperative scarring during wound healing. Two agents in common use are mitomycin C (MMC) and 5-Fluorouracil (5-FU). OBJECTIVES: To assess the effects of MMC compared to 5-FU as an antimetabolite adjunct in trabeculectomy surgery. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015 Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to October 2015), EMBASE (January 1980 to October 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to October 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 2 October 2015. SELECTION CRITERIA: We included randomised controlled trials where wound healing had been modified with MMC compared to 5-FU. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials and collected data. The primary outcome was failure of a functioning trabeculectomy one year after surgery. Secondary outcomes included mean intraocular pressure at one year. We considered three subgroups: high risk of trabeculectomy failure (people with previous glaucoma surgery, extracapsular cataract surgery, African origin and people with secondary glaucoma or congenital glaucoma); medium risk of trabeculectomy failure (people undergoing trabeculectomy with extracapsular cataract surgery) and low risk of trabeculectomy failure (people who have received no previous surgical eye intervention). MAIN RESULTS: We identified 11 trials that enrolled 687 eyes of 679 participants. The studies were conducted in the United States, Europe, Asia and Africa. Five studies enrolled participants at low risk of trabeculectomy failure, five studies enrolled participants at high risk of failure, and one study enrolled people with both high and low risk of failure. None of the included trials enrolled participants with combined trabeculectomy/cataract surgery.We considered one study to be at low risk of bias in all domains, six studies to be at high risk of bias in one or more domains, and the remaining four studies to be at an unclear risk of bias in all domains.The risk of failure of trabeculectomy at one year after surgery was less in those participants who received MMC compared to those who received 5-FU, however the confidence intervals were wide and are compatible with no effect (risk ratio (RR) 0.54, 95% confidence interval (CI) 0.30 to 1.00; studies = 11; I(2) = 40%). There was no evidence for any difference between groups at high and low risk of failure (test for subgroup differences P = 0.69).On average, people treated with MMC had lower intraocular pressure at one year (mean difference (MD) -3.05 mmHg, 95% CI -4.60 to -1.50), but the studies were inconsistent (I(2) = 52%). The size of the effect was greater in the high-risk group (MD -4.18 mmHg, 95% CI -6.73 to -1.64) compared to the low-risk group (MD -1.72 mmHg, 95% CI -3.28 to -0.16), but again the test for interaction was not statistically significant (P = 0.11).Similar proportions of eyes treated with MMC lost 2 or more lines of visual acuity one year after surgery compared to 5-FU, but the confidence intervals were wide (RR 1.05, 95% CI 0.54 to 2.06).Adverse events occurred relatively rarely, and estimates of effect were generally imprecise. There was some evidence for less epitheliopathy in the MMC group (RR 0.23, 95% CI 0.11 to 0.47) and less hyphaema in the MMC group (RR 0.62, 95% CI 0.42 to 0.91).None of the studies reported quality of life.Overall, we graded the quality of the evidence as low largely because of risk of bias in the included studies and imprecision in the estimate of effect. AUTHORS' CONCLUSIONS: We found low-quality evidence that MMC may be more effective in achieving long-term lower intraocular pressure than 5-FU. Further comparative research on MMC and 5-FU is needed to enhance reliability and validity of the results shown in this review. Furthermore, the development of new agents that control postoperative scar tissue formation without side effects would be valuable and is justified by the results of this review.

William John Adie: the man behind the syndrome.

William John Adie was an Australian neurologist in the early 20th century responsible for extensively describing the tonically dilated pupil associated with absent deep tendon reflexes - both features of a syndrome that now bears his name. In addition to other neurological syndromes, he was also significant in delineating narcolepsy through his clinical essays and case series. His ophthalmic and neurologic contributions have served the test of time and played an important role in the modern understanding of Adie syndrome and narcolepsy. This report reviews Adie's medical contributions, extensive descriptions of Adie syndrome, and provides a brief biographical account of his life.