Initial experience using a femtosecond laser cataract surgery system at a UK National Health Service cataract surgery day care centre

© 2019 The Author(s). This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/OBJECTIVES: To describe the initial outcomes following installation of a cataract surgery laser system.SETTING: National Health Service cataract surgery day care unit in North London, UK.PARTICIPANTS: 158 eyes of 150 patients undergoing laser-assisted cataract surgery.INTERVENTIONS: Laser cataract surgery using the AMO Catalys femtosecond laser platform.PRIMARY AND SECONDARY OUTCOME MEASURES: PRIMARY OUTCOME MEASURE: intraoperative complications including anterior and posterior capsule tears.SECONDARY OUTCOME MEASURES: docking to the laser platform, successful treatment delivery, postoperative visual acuities.RESULTS: Mean case age was 67.7±10.8 years (range 29-88 years). Docking was successful in 94% (148/158 cases), and in 4% (6/148 cases) of these, the laser delivery was aborted part way during delivery due to patient movement. A total of 32 surgeons, of grades from junior trainee to consultant, performed the surgeries. Median case number per surgeon was 3 (range from 1-20). The anterior capsulotomy was complete in 99.3% of cases, there were no anterior capsule tears (0%). There were 3 cases with posterior capsule rupture requiring anterior vitrectomy, and 1 with zonular dialysis requiring anterior vitrectomy (4/148 eyes, 2.7%). These 4 cases were performed by trainee surgeons, and were either their first laser cataract surgery (2 surgeons) or their first and second laser cataract surgeries (1 surgeon).CONCLUSIONS: Despite the learning curve, docking and laser delivery were successfully performed in almost all cases, and surgical complication rates and visual outcomes were similar to those expected based on national data. Complications were predominately confined to trainee surgeons, and with the exception of intraoperative pupil constriction appeared unrelated to the laser-performed steps.Peer reviewe

An inter-comparison of Arctic synoptic scale storms between four global reanalysis datasets

The Arctic is becoming more accessible as sea ice extent continues to decline, resulting in higher human exposure to Arctic storms. This study compares Arctic storm characteristics between the ECMWF-Interim Reanalysis, 55-year Japanese Reanalysis, NASA-Modern Era Retrospective Analysis for Research and Applications Version 2 and National Centre for Environmental Prediction-Climate Forecast System Reanalysis datasets between 1980 and 2017, in winter (DJF) and summer (JJA). It is shown that Arctic storm characteristics are sensitive to the variable used for storm tracking. Arctic storm frequency is found to be similar in summer and winter when using sea level pressure minima to track Arctic storms, whereas, the storm frequency is found to be higher in winter than summer when using 850 hPa relative vorticity to track storms, based on using the same storm tracking algorithm. It is also found that there are no significant trends in Arctic storm characteristics between 1980 and 2017. Given the sparsity of observations in the Arctic, it might be expected that there are large differences in Arctic storm characteristics between the reanalysis datasets. Though, some similar Arctic storm characteristics are found between the reanalysis datasets, it is found that the differences in Arctic storm characteristics between the reanalysis datasets are generally higher in winter than in summer. Overall, the results show that there are differences in Arctic storm characteristics between reanalysis datasets, but even larger differences can arise between using 850 hPa relative vorticity or mean sea level pressure as the storm tracking variable, which adds to the uncertainty associated with current Arctic storm characteristics

Changes in UK ophthalmology surgical training: analysis of cumulative surgical experience 2009-2015.

OBJECTIVE: To investigate changes in the patterns of cumulative surgical experience for ophthalmologists in the UK following the introduction of a new national training scheme. DESIGN: Retrospective review of all surgical training records submitted to the UK Royal College of Ophthalmologists by trainees for the award of Certificate of Completion of Training (CCT) for the period 2009-2015. SETTING: Secondary level care, UK. PARTICIPANTS: 539 trainees achieving CCT over the 7-year study period. INTERVENTIONS: Higher specialist training or ophthalmology specialist training. OUTCOME MEASURES: Number of CCT awards by years and procedures performed for cataract surgery, strabismus, corneal grafts, vitreoretinal (VR) procedures, oculoplastics and glaucoma. RESULTS: Cataract surgical experience showed little change with median number performed/performed supervised (P/PS) 592, IQR: 472-738; mean: 631. Similarly, the median number of strabismus (P/PS 34), corneal grafts (assisted, 9) and VR procedures (assisted, 34) appeared constant. There was a trend towards increasing surgical numbers for oculoplastics (median 116) and glaucoma (57). Overall case numbers for ophthalmic specialist training (OST) trainees (7-year training programme) were higher than higher surgical training (HST) trainees (4.5-year programme) with the exception of squint (P/PS), corneal grafts (P/PS) and VR cases (P/PS). CONCLUSIONS: Overall case numbers reported at time of CCT application appear stable or with a marginal trend towards increasing case numbers. HST (4.5-year programme) case numbers do not include those performed before entry to HST, and although case numbers tended to be higher for OST trainees (7-year programme) compared with HST trainees, they were not proportionately so

Laser-assisted cataract surgery versus standard ultrasound phacoemulsification cataract surgery.

BACKGROUND: Cataract is the leading cause of blindness in the world, and cataract surgery is one of the most commonly performed operations in the Western world. Preferred surgical techniques have changed dramatically over the past half century with associated improvements in outcomes and safety. Femtosecond laser platforms that can accurately and reproducibly perform key steps in cataract surgery, including corneal incisions, capsulotomy and lens fragmentation, are now available. The potential advantages of laser-assisted surgery are broad, and include greater safety and better visual outcomes through greater precision and reproducibility. OBJECTIVES: To compare the effectiveness of laser-assisted cataract surgery with standard ultrasound phacoemulsification cataract surgery by gathering evidence on safety from randomised controlled trials (RCTs). SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 4), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to May 2016), EMBASE (January 1980 to May 2016), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to May 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) and the U.S. Food and Drugs Administration (FDA) website (www.fda.gov). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 10 May 2016. SELECTION CRITERIA: We included randomised controlled trials where laser-assisted cataract surgery was compared to standard ultrasound phacoemulsification cataract surgery. We graded the certainty of the evidence using GRADE. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results, assessed risk of bias and extracted data using the standard methodological procedures expected by Cochrane. The primary outcome for this review was intraoperative complications in the operated eye, namely anterior capsule and posterior capsule tears. The secondary outcomes were visual acuity (corrected distance visual acuity (CDVA) and uncorrected distance visual acuity (UDVA)), refractive outcomes, quality of vision (as measured by any validated visual function score), postoperative complications and cost-effectiveness. MAIN RESULTS: We included 16 RCTs conducted in Germary, Hungary, Italy, India, China and Brazil that enrolled a total of 1638 eyes of 1245 adult participants. Overall, the studies were at unclear or high risk of bias. In 11 of the studies the authors reported financial links with the manufacturer of the laser platform evaluated in their studies. Five of the studies were within-person (paired-eye) studies with one eye allocated to one procedure and the other eye allocated to the other procedure. These studies were reported ignoring the paired nature of the data.The number of anterior capsule and posterior capsule tears reported in the included studies for both laser cataract surgery and manual phacoemulsification cataract surgery were low. There were four anterior capsule tears and one posterior capsule tear in 1076 eyes reported in 10 studies (2 anterior capsule tears in laser arms, 2 anterior capsule tears and 1 posterior capsule tear in standard phacoemulsification arms). We are very uncertain as to the effect of laser-assisted surgery compared to standard phacoemulsification surgery with respect to these two outcomes. For postoperative cystoid macular oedema and elevated postoperative intraocular pressures, again the evidence was inconclusive (odds ratio (OR) 0.58, 95% confidence interval (CI) 0.20 to 1.68; 957 eyes, 9 studies, low certainty evidence; and OR 0.57, 95% CI 0.11 to 2.86; 903 eyes, 8 studies, low certainty evidence).We found little evidence of any important difference in postoperative visual acuity between laser-assisted and standard phacoemulsification arms. There was a small advantage for laser-assisted cataract surgery at six months in CDVA. However, the mean difference (MD) was -0.03 logMAR (95% CI -0.05 to -0.00; 224 eyes, 3 studies, low certainty evidence) which is equivalent to 1.5 logMAR letters and is therefore, clinically insignificant. No studies reported patient-reported outcome measures such as visual function.There were no data reported on costs or resource use but three studies reported the time taken to do the surgery. There was little evidence of any major difference between the two procedures in this respect (MD 0.1 minutes, 95% CI -0.02 to 0.21; 274 eyes, low certainty evidence). AUTHORS' CONCLUSIONS: The evidence from the 16 randomised controlled trials RCTs included in this review could not determine the equivalence or superiority of laser-assisted cataract surgery compared to standard manual phacoemulsification for our chosen outcomes due to the low to very low certainty of the evidence available from these studies. As complications occur rarely, large, adequately powered, well designed, independent RCTs comparing the safety and efficacy of laser-assisted cataract surgery with standard phacoemulsification cataract surgery are needed. Standardised reporting of complications and visual and refractive outcomes for cataract surgery would facilitate future synthesis. Data on patient-reported outcomes and cost-effectiveness are needed. Paired-eye studies should be analysed and reported appropriately

Using genetics to investigate the association between lanosterol and cataract

Background: Cataract is one of the most prevalent causes of blindness worldwide. Whilst surgery is the primary treatment for cataracts, it is not always an available option, particularly in developing countries. Non-surgical methods of treatment would increase treatment availability for more patients. Several studies have investigated how topical application of oxysterols, such as lanosterol, may break down aggregated proteins and restore lens transparency. However, the results are conflicting and inconclusive.Aim: In this study, we focus on combining genetic evidence for associations between lanosterol related genetic variation and cataract to explore whether lanosterol is a potentially suitable drug treatment option.Method: Using data from 45,449 available cataract cases from the UK Biobank, with participant ages ranging from 40–69, we conducted a genetic association study (GWAS) to assess the risk of cataract. Cataract cases were defined using diagnostic and operation codes. We focused on genetic variants in the lanosterol synthase gene region. We also compared our results with previously published genetic associations of phytosterol-to-lanosterol ratios. Finally, we performed a genetic risk score analysis to test the association between lanosterol within the cholesterol synthesis pathway and the risk of cataract.Results: No statistically significant single nucleotide polymorphisms (SNPs) associations with cataract were observed in the gene region of lanosterol synthase at a multiple testing adjusted significance threshold of p < 0.05/13. The comparison between cataract risk and genetic association of 8 phytosterol-to-lanosterol GWAS results also showed no evidence to support lanosterol’s protective properties for cataract risk. No statistically significant association was found between the lanosterol within the cholesterol synthesis pathway genetic risk score and cataract outcomes (OR = 1.002 p = 0.568).Conclusion: There was no evidence observed for genetic associations between lanosterol and cataract risk. Our results do not support lanosterol’s potential role in treating cataracts. Further research may be needed to address the effect of lanosterol on specific cataract subtypes

Risk factors for the evolutionary emergence of pathogens

Recent outbreaks of novel infectious diseases (e.g. SARS, influenza H1N1) have highlighted the threat of cross-species pathogen transmission. When first introduced to a population, a pathogen is often poorly adapted to its new host and must evolve in order to escape extinction. Theoretical arguments and empirical studies have suggested various factors to explain why some pathogens emerge and others do not, including host contact structure, pathogen adaptive pathways and mutation rates. Using a multi-type branching process, we model the spread of an introduced pathogen evolving through several strains. Extending previous models, we use a network-based approach to separate host contact patterns from pathogen transmissibility. We also allow for arbitrary adaptive pathways. These generalizations lead to novel predictions regarding the impact of hypothesized risk factors. Pathogen fitness depends on the host population in which it circulates, and the ‘riskiest’ contact distribution and adaptive pathway depend on initial transmissibility. Emergence probability is sensitive to mutation probabilities and number of adaptive steps required, with the possibility of large adaptive steps (e.g. simultaneous point mutations or recombination) having a dramatic effect. In most situations, increasing overall mutation probability increases the risk of emergence; however, notable exceptions arise when deleterious mutations are available

Cochrane Corner: immediate sequential bilateral surgery versus delayed sequential bilateral surgery for cataracts.

The recently published Cochrane Review by Dickman et al. evaluated safety, clinical outcomes, cost-effectiveness and patient-reported outcomes of immediate sequential bilateral cataract surgery (ISBCS) compared to delayed sequential bilateral cataract surgery (DSBCS). A total of 14 studies were included involving 276,260 patients (7384 for ISBCS and 268,876 for DSBCS); comprising two randomised controlled trials (RCTs), seven non-randomised studies (NRSs) and six economic evaluations (one study being both a NRS and an economic evaluation). The review authors concluded that there were likely no clinically important differences in outcomes between ISBCS and DSBCS, although the limited quantity and quality of evidence provided only low- to very low-certainty regarding this lack of difference for most outcomes of interest

Narrative-based computational modelling of the Gp130/JAK/STAT signalling pathway.

BACKGROUND: Appropriately formulated quantitative computational models can support researchers in understanding the dynamic behaviour of biological pathways and support hypothesis formulation and selection by "in silico" experimentation. An obstacle to widespread adoption of this approach is the requirement to formulate a biological pathway as machine executable computer code. We have recently proposed a novel, biologically intuitive, narrative-style modelling language for biologists to formulate the pathway which is then automatically translated into an executable format and is, thus, usable for analysis via existing simulation techniques. RESULTS: Here we use a high-level narrative language in designing a computational model of the gp130/JAK/STAT signalling pathway and show that the model reproduces the dynamic behaviour of the pathway derived by biological observation. We then "experiment" on the model by simulation and sensitivity analysis to define those parameters which dominate the dynamic behaviour of the pathway. The model predicts that nuclear compartmentalisation and phosphorylation status of STAT are key determinants of the pathway and that alternative mechanisms of signal attenuation exert their influence on different timescales. CONCLUSION: The described narrative model of the gp130/JAK/STAT pathway represents an interesting case study showing how, by using this approach, researchers can model biological systems without explicitly dealing with formal notations and mathematical expressions (typically used for biochemical modelling), nevertheless being able to obtain simulation and analysis results. We present the model and the sensitivity analysis results we have obtained, that allow us to identify the parameters which are most sensitive to perturbations. The results, which are shown to be in agreement with existing mathematical models of the gp130/JAK/STAT pathway, serve us as a form of validation of the model and of the approach itself

Cheminformatics Analysis of Assertions Mined from Literature That Describe Drug-Induced Liver Injury in Different Species

Drug Induced Liver Injury (DILI) is one of the main causes of drug attrition. The ability to predict the liver effects of drug candidates from their chemical structure is critical to help guiding experimental drug discovery projects towards safer medicines. In this study, we have compiled a dataset of 951 compounds reported to produce a wide range of effects in the liver in different species, comprising humans, rodents, and non-rodents. The liver effects for this dataset were obtained as assertional meta-data, generated from MEDLINE abstracts using a unique combination of lexical and linguistic methods and ontological rules. We have analyzed this dataset using conventional cheminformatics approaches and addressed several questions pertaining to cross-species concordance of liver effects, chemical determinants of liver effects in humans, and the prediction of whether a given compound is likely to cause a liver effect in humans. We found that the concordance of liver effects was relatively low (ca. 39–44%) between different species raising the possibility that species specificity could depend on specific features of chemical structure. Compounds were clustered by their chemical similarity, and similar compounds were examined for the expected similarity of their species-dependent liver effect profiles. In most cases, similar profiles were observed for members of the same cluster, but some compounds appeared as outliers. The outliers were the subject of focused assertion re-generation from MEDLINE, as well as other data sources. In some cases, additional biological assertions were identified which were in line with expectations based on compounds' chemical similarity. The assertions were further converted to binary annotations of underlying chemicals (i.e., liver effect vs. no liver effect), and binary QSAR models were generated to predict whether a compound would be expected to produce liver effects in humans. Despite the apparent heterogeneity of data, models have shown good predictive power assessed by external five-fold cross validation procedures. The external predictive power of binary QSAR models was further confirmed by their application to compounds that were retrieved or studied after the model was developed. To the best of our knowledge, this is the first study for chemical toxicity prediction that applied QSAR modeling and other cheminformatics techniques to observational data generated by the means of automated text mining with limited manual curation, opening up new opportunities for generating and modeling chemical toxicology data