A Population-Based Ultra-Widefield Digital Image Grading Study for Age-Related Macular Degeneration-Like Lesions at the Peripheral Retina.

Our understanding of the relevance of peripheral retinal abnormalities to disease in general and in age-related macular degeneration (AMD) in particular is limited by the lack of detailed peripheral imaging studies. The purpose of this study was to develop image grading protocols suited to ultra-widefield imaging (UWFI) in an aged population

Identification of increased blue light reflectivity in macular telangiectasia type 2 using scanning laser ophthalmoscopy versus red-free fundus photography

PURPOSE: To compare two modalities used for detection of the characteristic parafoveal hyperreflective area seen in macular telangiectasia Type 2. METHODS: Scanning laser ophthalmoscope blue light reflectance was compared with red-free fundus photography imaging. Images were obtained as part of the international Natural History Study of Macular Telangiectasia (MacTel Study). RESULTS: The hyperreflective area can more frequently be seen with scanning laser ophthalmoscope blue light reflectance than with red-free imaging. CONCLUSION: Detection of the hyperreflective area might help to identify macular telangiectasia in earlier disease stages. Scanning laser ophthalmoscope blue light reflectance should be preferred as a diagnostic tool when the suspicion of macular telangiectasia arises. However, red-free imaging offers a viable option to scanning laser ophthalmoscope blue light reflectance when good quality is achieved

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

Zinc Nutrition and Inflammation in the Aging Retina

Zinc is an essential nutrient for human health. It plays key roles in maintaining protein structure and stability, serves as catalytic factor for many enzymes, and regulates diverse fundamental cellular processes. Zinc is important in affecting signal transduction and, in particular, in the development and integrity of the immune system, where it affects both innate and adaptive immune responses. The eye, especially the retina‐choroid complex, has an unusually high concentration of zinc compared to other tissues. The highest amount of zinc is concentrated in the retinal pigment epithelium (RPE) (RPE‐choroid, 292 ± 98.5 µg g−1 dry tissue), followed by the retina (123 ± 62.2 µg g−1 dry tissue). The interplay between zinc and inflammation has been explored in other parts of the body but, so far, has not been extensively researched in the eye. Several lines of evidence suggest that ocular zinc concentration decreases with age, especially in the context of age‐related disease. Thus, a hypothesis that retinal function could be modulated by zinc nutrition is proposed, and subsequently trialled clinically. In this review, the distribution and the potential role of zinc in the retina‐choroid complex is outlined, especially in relation to inflammation and immunity, and the clinical studies to date are summarized

Electrocardiographic safety evaluation of dihydroartemisinin piperaquine in the treatment of uncomplicated falciparum malaria.

Dihydroartemisinin-piperaquine (DP) could become a leading fixed combination malaria treatment worldwide. Although there is accumulating evidence of efficacy and safety from clinical trials, data on cardiotoxicity are limited. In two randomized controlled trials in Thailand, 56 patients had ECGs performed before treatment, 4 hours after the first dose, and 4 hours after the last dose. The mean (95% CI) changes in QTc interval (Bazett's correction) were 2 (-6 to 9) ms and 14 (7 to 21) ms, respectively. These small changes on the third day of treatment are similar to those observed elsewhere in the convalescent phase following antimalarial treatment with drugs known to have no cardiac effects and are therefore likely to result from recovery from acute malaria and not the treatment given. At therapeutic doses, DP does not have clinically significant effects on the electrocardiogram

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

The expected burden of mesothelioma mortality in Great Britain from 2002 to 2050

The British mesothelioma register contains all deaths from 1968 to 2001 where mesothelioma was mentioned on the death certificate. These data were used to predict the future burden of mesothelioma mortality in Great Britain. Poisson regression analysis was used to model male mesothelioma deaths from 1968 to 2001 as a function of the rise and fall of asbestos exposure during the 20th century, and hence to predict numbers of male deaths in the years 2002–2050. The annual number of mesothelioma deaths in Great Britain has risen increasingly rapidly from 153 deaths in 1968 to 1848 in 2001 and, using our preferred model, is predicted to peak at around 1950 to 2450 deaths per year between 2011 and 2015. Following this peak, the number of deaths is expected to decline rapidly. The eventual death rate will depend on the background level and any residual asbestos exposure. Between 1968 and 2050, there will have been approximately 90 000 deaths from mesothelioma in Great Britain, 65 000 of which will occur after 2001

Health record hiccups—5,526 real-world time series with change points labelled by crowdsourced visual inspection

Background: Large routinely collected data such as electronic health records (EHRs) are increasingly used in research, but the statistical methods and processes used to check such data for temporal data quality issues have not moved beyond manual, ad hoc production and visual inspection of graphs. With the prospect of EHR data being used for disease surveillance via automated pipelines and public-facing dashboards, automation of data quality checks will become increasingly valuable. / Findings: We generated 5,526 time series from 8 different EHR datasets and engaged >2,000 citizen-science volunteers to label the locations of all suspicious-looking change points in the resulting graphs. Consensus labels were produced using density-based clustering with noise, with validation conducted using 956 images containing labels produced by an experienced data scientist. Parameter tuning was done against 670 images and performance calculated against 286 images, resulting in a final sensitivity of 80.4% (95% CI, 77.1%–83.3%), specificity of 99.8% (99.7%–99.8%), positive predictive value of 84.5% (81.4%–87.2%), and negative predictive value of 99.7% (99.6%–99.7%). In total, 12,745 change points were found within 3,687 of the time series. / Conclusions: This large collection of labelled EHR time series can be used to validate automated methods for change point detection in real-world settings, encouraging the development of methods that can successfully be applied in practice. It is particularly valuable since change point detection methods are typically validated using synthetic data, so their performance in real-world settings cannot be assumed to be comparable. While the dataset focusses on EHRs and data quality, it should also be applicable in other fields

Retinal phenotyping of variants of Alzheimer's disease using ultra-widefield retinal images

Background: Posterior cortical atrophy (PCA) is the most common atypical variant of Alzheimer's disease (AD). Changes associated with PCA in the brain affect the visual cortex, but little is known about retinal changes in PCA. In this study, we explored retinal phenotypic variations in typical AD (tAD) and PCA. Methods: Retinal phenotyping was carried out on ultra-widefield (UWF) images of 69 control, 24 tAD, and 25 PCA participants. Results: Individuals with tAD (odds ratio [OR] = 2.76 [confidence interval (CI):1.24 to 6.10], P = .012) and PCA (OR = 3.40 [CI:1.25 to 9.22], P = .016) were more likely phenotyped as hard drusen. tAD (OR = 0.34 [CI:0.12 to 0.92], P = .035) were less likely to have soft drusen compared to control. Almost 3-fold increase in reticular pseudodrusen formation in tAD (OR = 2.93 [CI:1.10 to 7.76], P = .030) compared to control was estimated. Discussion: Studying the peripheral retina may contribute to a better understanding of differences in retinal phenotypes of different AD variants