Interventions to control myopia progression in children: protocol for an overview of systematic reviews and meta-analyses.

Background Myopia is a common visual disorder with increasing prevalence among developed countries of the world. Myopia constitutes a substantial risk factor for several ocular conditions that can lead to blindness. The purpose of this study is to conduct an overview of systematic reviews and meta-analyses in order to identify and appraise robust research evidence regarding the management of myopia progression in children and adolescents. Methods A literature search will be conducted in MEDLINE, EMBASE, The Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE), and Health Technology Assessment (HTA) Database via Centre for Reviews and Dissemination (CRD). We will search for systematic reviews or meta-analyses that examine optical or pharmaceutical modalities for myopia control. Two independent overview authors will screen the titles and abstracts against the eligibility criteria. Individual study’s methodological quality and quality of evidence for each outcome of interest will be assessed by two independent authors using the ROBIS tool and GRADE rating, respectively. In cases of disagreement, consensus will be reached with the help of a third author. Our primary outcomes will be the mean change in refractive error, mean axial length change, and adverse events. A citation matrix will be generated, and the corrected covered area (CCA) will be estimated, in order to identify overlapping primary studies. Possible meta-biases and measures of heterogeneity will be described, and cases of dual co-authorship will be identified and discussed. If any recently published randomized controlled trials (RCTs) are detected, these will be appraised and their findings will be presented. An overall summary of outcomes will be provided using descriptive statistics and will be supplemented by narrative synthesis. Discussion This overview will examine the high level of existing evidence for treatment of myopia progression. Efficient interventions will be identified, and side effects will be reported. The expected benefit is that all robust recent research evidence will be compiled in a single study. The results may inform future research in this area, which should provide insight into the appropriate regimes for the administration of these modalities and contribute to future guideline development

Long-term efficacy of botulinum toxin A for treatment of blepharospasm,hemifacial spasm, and spastic entropion: a multicentre study using two drug-dose escalation indexes

PURPOSE: To investigate the long-term effectiveness and safety of botulinum neurotoxin A (BoNT-A) treatment in patients with blepharospasm (BEB), hemifacial spasm (HFS), and entropion (EN) and to use for the first time two modified indexes, 'botulin toxin escalation index-U' (BEI-U) and 'botulin toxin escalation index percentage' (BEI-%), in the dose-escalation evaluation. METHODS: All patients in this multicentre study were followed for at least 10 years and main outcomes were clinical efficacy, duration of relief, BEI-U and BEI-%, and frequency of adverse events. RESULTS: BEB, HFS, and EN patients received a mean BoNT-A dose with a significant inter-group difference (P<0.0005, respectively). The mean (+/-SD) effect duration was statistically different (P=0.009) among three patient groups. Regarding the BoNT-A escalation indexes, the mean (+/-SD) values of BEI-U and BEI-% were statistically different (P=0.035 and 0.047, respectively) among the three groups. In BEB patients, the BEI-% was significantly increased in younger compared with older patients (P=0.008). The most frequent adverse events were upper lid ptosis, diplopia, ecchymosis, and localized bruising. CONCLUSIONS: This long-term multicentre study supports a high efficacy and good safety profile of BoNT-A for treatment of BEB, HFS, and EN. The BEI indexes indicate a significantly greater BoNT-A-dose escalation for BEB patients compared with HFS or EN patients and a significantly greater BEI-% in younger vsolder BEB patients. These results confirm a greater efficacy in the elderly and provide a framework for long-term studies with a more flexible and reliable evaluation of drug-dose escalation

Nuclear Reprogramming: Kinetics of Cell Cycle and Metabolic Progression as Determinants of Success

Establishment of totipotency after somatic cell nuclear transfer (NT) requires not only reprogramming of gene expression, but also conversion of the cell cycle from quiescence to the precisely timed sequence of embryonic cleavage. Inadequate adaptation of the somatic nucleus to the embryonic cell cycle regime may lay the foundation for NT embryo failure and their reported lower cell counts. We combined bright field and fluorescence imaging of histone H2b-GFP expressing mouse embryos, to record cell divisions up to the blastocyst stage. This allowed us to quantitatively analyze cleavage kinetics of cloned embryos and revealed an extended and inconstant duration of the second and third cell cycles compared to fertilized controls generated by intracytoplasmic sperm injection (ICSI). Compared to fertilized embryos, slow and fast cleaving NT embryos presented similar rates of errors in M phase, but were considerably less tolerant to mitotic errors and underwent cleavage arrest. Although NT embryos vary substantially in their speed of cell cycle progression, transcriptome analysis did not detect systematic differences between fast and slow NT embryos. Profiling of amino acid turnover during pre-implantation development revealed that NT embryos consume lower amounts of amino acids, in particular arginine, than fertilized embryos until morula stage. An increased arginine supplementation enhanced development to blastocyst and increased embryo cell numbers. We conclude that a cell cycle delay, which is independent of pluripotency marker reactivation, and metabolic restraints reduce cell counts of NT embryos and impede their development

Prevalence of myopia at 9 months in infants with high-risk prethreshold retinopathy of prematurity

PURPOSE: To examine the prevalence of myopia and high myopia at 9 months corrected age in premature infants who participated in the multicenter randomized trial of Early Treatment for Retinopathy of Prematurity (ETROP). DESIGN: Randomized, controlled clinical trial. PARTICIPANTS: Four hundred one infants with birth weights of or =15%) of poor structural outcomes without treatment, based on the risk management for ROP program. INTERVENTION: Infants with bilateral high-risk prethreshold ROP (n = 317) had 1 eye randomized to early treatment, and the fellow eye was managed conventionally. In asymmetric cases (n = 84), the eye with high-risk prethreshold ROP was randomized to early treatment or conventional management (control). Eyes randomized to early treatment at high-risk prethreshold ROP and eyes randomized to conventional management in which threshold ROP developed received peripheral retinal photocoagulation or cryotherapy. Conventionally managed eyes in which threshold ROP did not develop were observed. Cycloplegic retinoscopy data were obtained at 9 months corrected age from 321 eyes treated early and 307 eyes managed conventionally. MAIN OUTCOME MEASURES: Prevalence of myopic (spherical equivalent > or = 0.25 diopters [D]) and highly myopic (> or =5.00 D) eyes in each group. RESULTS: The prevalence of myopia (64.5% vs. 69.4%; P = 0.06) and high myopia (25.5% vs. 28.3%; P = 0.20) was similar between eyes treated at high-risk prethreshold and high-risk prethreshold eyes managed conventionally. Among high-risk eyes managed conventionally, the prevalence of myopia (78.2% vs. 53.3%) and high myopia (37.6% vs. 11.2%) was higher when threshold ROP developed than when regression without treatment occurred. Among eyes treated at high-risk prethreshold ROP, the prevalence of myopia (93.3% vs. 91.7% vs. 60.6%) and of high myopia (53.3% vs. 33.3% vs. 20.8%) was higher in eyes with abnormal angle of temporal retinal vessels or macular ectopia than in eyes with no retinal residua. This also held true for conventionally managed eyes. CONCLUSIONS: Early treatment at high-risk prethreshold did not place eyes at greater risk of myopia and high myopia than did conventional management of eyes with high-risk prethreshold ROP