Quantitative Analysis of Hyperautofluorescent Rings to Characterize the Natural History and Progression in Rpgr-associated Retinopathy

PURPOSE: Quantitative analysis of hyperautofluorescent rings and progression in subjects with retinitis pigmentosa associated with retinitis pigmentosa GTPase regulator (RPGR) gene mutations. METHODS: Prospective observational study of 46 subjects. Ring area, horizontal and vertical diameter measurements taken from outer and inner ring borders. Intraobserver repeatability, baseline measurements, progression rates, interocular symmetry, and association with age and genotype were investigated. RESULTS: Baseline ring area was 11.8 ± 13.4 mm and 11.4 ± 13.2 mm for right and left eyes, respectively, with very strong interocular correlation (r = 0.9398; P < 0.0001). Ring area constriction was 1.5 ± 2.0 mm/year and 1.3 ± 1.9 mm/year for right and left eyes, respectively, with very strong interocular correlation (r = 0.878, P < 0.0001). Baseline ring area and constriction rate correlated negatively with age (r = -0.767; P < 0.0001 and r = -0.644, P < 0.0001, respectively). Constriction rate correlated strongly with baseline area (r = 0.850, P < 0.0001). Age, but not genotype, exerted a significant effect on constriction rates (P < 0.0001), with greatest rates of progression seen in younger subjects. An exponential decline overall was found. CONCLUSION: This study provides disease-specific baseline values and progression rates together with a repeatability assessment of fundus autofluorescence metrics. Our findings can guide future treatment trials and contribute to the clinical care of patients with RPGR-associated retinitis pigmentosa

Role of advanced technology in the detection of sight-threatening eye disease in a UK community setting.

Background/aims: To determine the performance of combinations of structural and functional screening tests in detecting sight-threatening eye disease in a cohort of elderly subjects recruited from primary care. Methods: 505 subjects aged ≥60 years underwent frequency doubling technology (FDT) perimetry, iVue optical coherence tomography (iWellness and peripapillary retinal nerve fibre layer (RNFL) scans) and intraocular pressure with the Ocular Response Analyzer, all performed by an ophthalmic technician. The reference standard was a full ophthalmic examination by an experienced clinician who was masked to the index test results. Subjects were classified as presence or absence of sight-threatening eye disease (clinically significant cataract, primary open-angle glaucoma, intermediate or advanced age-related macular degeneration and significant diabetic retinopathy). Univariate and multivariate logistic regression analyses were used to determine the association between abnormal screening test results and the presence of sight-threatening eye disease. Results: 171 subjects (33.8%) had one or more sight-threatening eye diseases. The multivariate analysis found significant associations with any of the target conditions for visual acuity of <6/12, an abnormal FDT and peripapillary RNFL thickness outside the 99% normal limit. The sensitivity of this optimised screening panel was 61.3% (95% CI 53.5 to 68.7), with a specificity of 78.8% (95% CI 74.0 to 83.1), a positive predictive value of 59.5% (95% CI 53.7 to 65.2) and an overall diagnostic accuracy of 72.9% (95% CI 68.8 to 76.8). Conclusions: A subset of screening tests may provide an accurate and efficient means of population screening for significant eye disease in the elderly. This study provides useful preliminary data to inform the development of further larger, multicentre screening studies to validate this screening panel

Agreement between image grading of conventional (45°) and ultra wide-angle (200°) digital images in the macula in the Reykjavik eye study.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldPURPOSE: To establish the agreement between image grading of conventional (45°) and ultra wide-angle (200°) digital images in the macula. METHODS: In 2008, the 12-year follow-up was conducted on 573 participants of the Reykjavik Eye Study. This study included the use of the Optos P200C AF ultra wide-angle laser scanning ophthalmoscope alongside Zeiss FF 450 conventional digital fundus camera on 121 eyes with or without age-related macular degeneration using the International Classification System. Of these eyes, detailed grading was carried out on five cases each with hard drusen, geographic atrophy and chorioretinal neovascularisation, and six cases of soft drusen. Exact agreement and κ-statistics were calculated. RESULTS: Comparison of the conventional and ultra wide-angle images in the macula showed an overall 96.43% agreement (κ=0.93) with no disagreement at end-stage disease; although in one eye chorioretinal neovascularisation was graded as drusenoid pigment epithelial detachment. Of patients with drusen only, the exact agreement was 96.1%. The detailed grading showed no clinically significant disagreement between the conventional 45° and 200° images. CONCLUSIONS: On the basis of our results, there is a good agreement between grading conventional and ultra wide-angle images in the macul

The role of adjuvant chemotherapy for patients with resected pancreatic cancer: Systematic review of randomized controlled trials and meta-analysis

Background: In patients undergoing surgery for resectable pancreatic cancer prognosis still remains poor. The role of adjuvant treatment strategies (including chemotherapy and chemoradiotherapy) following resection of pancreatic cancer remains controversial. Methods: A Medline-based literature search was undertaken to identify randomized controlled trials that evaluated adjuvant chemotherapy after complete macroscopic resection for cancer of the exocrine pancreas. Five trials of adjuvant chemotherapy were eligible and critically reviewed for this article. A meta-analysis (based on published data) was performed with survival (median survival time and 5-year survival rate) being the primary endpoint. Results: For the meta-analysis, 482 patients were allocated to the chemotherapy group and 469 patients to the control group. The meta-analysis estimate for prolongation of median survival time for patients in the chemotherapy group was 3 months (95% CI 0.3-5.7 months, p = 0.03). The difference in 5-year survival rate was estimated with 3.1% between the chemotherapy and the control group (95% CI -4.6 to 10.8%, p > 10.05). Conclusion: Currently available data from randomized trials indicate that adjuvant chemotherapy after resection of pancreatic cancer may substantially prolong disease-free survival and cause a moderate increase in overall survival. In the current meta-analysis, a significant survival benefit was only seen with regard to median survival, but not for the 5-year survival rate. The optimal chemotherapy regimen in the adjuvant setting as well as individualized treatment strategies (also including modern chemoradiotherapy regimens) still remain to be defined. Copyright (C) 2008 S. Karger AG, Basel

Cone photoreceptor definition on adaptive optics retinal imaging

To quantitatively analyse cone photoreceptor matrices on images captured on an adaptive optics (AO) camera and assess their correlation to well-established parameters in the retinal histology literature

The relative importance of large problems far away versus small problems closer to home: insights into limiting the spread of antimicrobial resistance in England

Background: To combat the spread of antimicrobial resistance (AMR), hospitals are advised to screen high-risk patients for carriage of antibiotic-resistant bacteria on admission. This often includes patients previously admitted to hospitals with a high AMR prevalence. However, the ability of such a strategy to identify introductions (and hence prevent onward transmission) is unclear, as it depends on AMR prevalence in each hospital, the number of patients moving between hospitals, and the number of hospitals considered ‘high risk’. / Methods: We tracked patient movements using data from the National Health Service of England Hospital Episode Statistics and estimated differences in regional AMR prevalences using, as an exemplar, data collected through the national reference laboratory service of Public Health England on carbapenemase-producing Enterobacteriaceae (CPE) from 2008 to 2014. Combining these datasets, we calculated expected CPE introductions into hospitals from across the hospital network to assess the effectiveness of admission screening based on defining high-prevalence hospitals as high risk. / Results: Based on numbers of exchanged patients, the English hospital network can be divided into 14 referral regions. England saw a sharp increase in numbers of CPE isolates referred to the national reference laboratory over 7 years, from 26 isolates in 2008 to 1649 in 2014. Large regional differences in numbers of confirmed CPE isolates overlapped with regional structuring of patient movements between hospitals. However, despite these large differences in prevalence between regions, we estimated that hospitals received only a small proportion (1.8%) of CPE-colonised patients from hospitals outside their own region, which decreased over time. / Conclusions: In contrast to the focus on import screening based on assigning a few hospitals as ‘high risk’, patient transfers between hospitals with small AMR problems in the same region often pose a larger absolute threat than patient transfers from hospitals in other regions with large problems, even if the prevalence in other regions is orders of magnitude higher. Because the difference in numbers of exchanged patients, between and within regions, was mostly larger than the difference in CPE prevalence, it would be more effective for hospitals to focus on their own populations or region to inform control efforts rather than focussing on problems elsewhere

Optical Coherence Tomography in the UK Biobank Study - Rapid Automated Analysis of Retinal Thickness for Large Population-Based Studies

PURPOSE: To describe an approach to the use of optical coherence tomography (OCT) imaging in large, population-based studies, including methods for OCT image acquisition, storage, and the remote, rapid, automated analysis of retinal thickness. METHODS: In UK Biobank, OCT images were acquired between 2009 and 2010 using a commercially available “spectral domain” OCT device (3D OCT-1000, Topcon). Images were obtained using a raster scan protocol, 6 mm x 6 mm in area, and consisting of 128 B-scans. OCT image sets were stored on UK Biobank servers in a central repository, adjacent to high performance computers. Rapid, automated analysis of retinal thickness was performed using custom image segmentation software developed by the Topcon Advanced Biomedical Imaging Laboratory (TABIL). This software employs dual-scale gradient information to allow for automated segmentation of nine intraretinal boundaries in a rapid fashion. RESULTS: 67,321 participants (134,642 eyes) in UK Biobank underwent OCT imaging of both eyes as part of the ocular module. 134,611 images were successfully processed with 31 images failing segmentation analysis due to corrupted OCT files or withdrawal of subject consent for UKBB study participation. Average time taken to call up an image from the database and complete segmentation analysis was approximately 120 seconds per data set per login, and analysis of the entire dataset was completed in approximately 28 days. CONCLUSIONS: We report an approach to the rapid, automated measurement of retinal thickness from nearly 140,000 OCT image sets from the UK Biobank. In the near future, these measurements will be publically available for utilization by researchers around the world, and thus for correlation with the wealth of other data collected in UK Biobank. The automated analysis approaches we describe may be of utility for future large population-based epidemiological studies, clinical trials, and screening programs that employ OCT imaging

Preoperative Posturing of Patients with Macula-On Retinal Detachment Reduces Progression Toward the Fovea

Purpose: Traditionally, preoperative posturing consisting of bed rest and positioning is prescribed to patients with macula-on retinal detachment (RD) to prevent RD progression and detachment of the fovea. Execution of such advice can be cumbersome and expensive. This study aimed to investigate if preoperative posturing affects the progression of RD. Design: Prospective cohort study. Participants: Ninety-eight patients with macula-on RD were included. Inclusion criteria were volume optical coherence tomography (OCT) scans could be obtained with sufficient quality; and the smallest distance from the fovea to the detachment border was 1.25 mm or more. Methods: Patients were admitted to the ward for bed rest in anticipation of surgery and were positioned on the side where the RD was mainly located. At baseline and before and after each interruption for meals or toilet visits, a 37°×45° OCT volume scan was performed using a wide-angle Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany). The distance between the nearest point of the RD border and fovea was measured using a custom-built measuring tool. Main Outcome Measures: The RD border displacement and the average RD border displacement velocity moving toward (negative) or away (positive) from the fovea were determined for intervals of posturing and interruptions. Results: The median duration of intervals of posturing was 3.0 hours (interquartile range [IQR], 1.8-14.0 hours; n = 202) and of interruptions 0.37 hours (IQR, 0.26-0.50 hours; n = 197). The median RD border displacement was 2 μm (IQR, -65 to +251 μm) during posturing and -61 μm (IQR, -140 to 0 μm) during interruptions, a statistically significant difference (P < 0.001, Mann-Whitney U test). The median RD border displacement velocity was +1 μm/hour (IQR, -21 to +49 μm/hour) during posturing and -149 μm/hour (IQR, -406 to +1 μm/hour) during interruptions, a statistically significant difference (P < 0.001). Conclusions: By making use of usual interruptions of preoperative posturing we were able to show, in a prospective and ethically acceptable manner, that RD stabilizes during posturing and progresses during interruptions in patients with macula-on RD. Preoperative posturing is effective in reducing progression of RD

Chromosomal Integration of the Klebsiella pneumoniae carbapenemase gene (blaKPC) in Klebsiella Species: Elusive but not Rare

Carbapenemase genes in Enterobacteriaceae are mostly described as being plasmid-associated. However, the genetic context of carbapenemase genes is not always confirmed in epidemiological surveys, and the frequency of their chromosomal integration is therefore unknown. A previously sequenced collection of blaKPC-positive Enterobacteriaceae from a single US institution (2007 2012; n=281 isolates, 182 patients) was analyzed to identify chromosomal insertions of Tn4401, the transposon most frequently harboring blaKPC. Using a combination of short- and long-read sequencing, we confirmed five independent chromosomal integration events from 6/182 (3%) patients, corresponding to 15/281 (5%) isolates. Three patients had isolates identified by peri-rectal screening and three had infections which were all successfully treated. When a single copy of blaKPC was in the chromosome one or both of the phenotypic carbapenemase tests were negative. All chromosomally integrated blaKPC were from Klebsiella spp., predominantly K. pneumoniae clonal group (CG)258, even though these represented only a small proportion of the isolates. Integration occurred via IS15-ΔI mediated transposition of a larger, composite region encompassing Tn4401 at one locus of chromosomal integration, seen in the same strain (K. pneumoniae ST340) in two patients. In summary, we identified five independent chromosomal integrations of blaKPC in a large outbreak, demonstrating that this is not a rare event. blaKPC was more frequently integrated into the chromosome of epidemic CG258 K. pneumoniae lineages (ST11, ST258, ST340), and was more difficult to detect by routine phenotypic methods in this context. The presence of chromosomally integrated blaKPC within successful, globally disseminated K. pneumoniae strains is therefore likely underestimated