ORCID Profile
0000-0001-5120-0086
Current Organisation
The University of Edinburgh
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Publisher: BMJ
Date: 04-2015
Publisher: Springer International Publishing
Date: 2022
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 29-08-2017
DOI: 10.1161/CIRCULATIONAHA.117.028433
Abstract: Ultrasmall superparamagnetic particles of iron oxide (USPIO) detect cellular inflammation on magnetic resonance imaging (MRI). In patients with abdominal aortic aneurysm, we assessed whether USPIO-enhanced MRI can predict aneurysm growth rates and clinical outcomes. In a prospective multicenter open-label cohort study, 342 patients with abdominal aortic aneurysm (diameter ≥40 mm) were classified by the presence of USPIO enhancement and were monitored with serial ultrasound and clinical follow-up for ≥2 years. The primary end point was the composite of aneurysm rupture or repair. Participants (85% male, 73.1±7.2 years) had a baseline aneurysm diameter of 49.6±7.7 mm, and USPIO enhancement was identified in 146 (42.7%) participants, absent in 191 (55.8%), and indeterminant in 5 (1.5%). During follow-up (1005±280 days), 17 (5.0%) abdominal aortic aneurysm ruptures, 126 (36.8%) abdominal aortic aneurysm repairs, and 48 (14.0%) deaths occurred. Compared with those without uptake, patients with USPIO enhancement have increased rates of aneurysm expansion (3.1±2.5 versus 2.5±2.4 mm/year, P =0.0424), although this was not independent of current smoking habit ( P =0.1993). Patients with USPIO enhancement had higher rates of aneurysm rupture or repair (47.3% versus 35.6% 95% confidence intervals, 1.1–22.2 P =0.0308). This finding was similar for each component of rupture (6.8% versus 3.7%, P =0.1857) or repair (41.8% versus 32.5%, P =0.0782). USPIO enhancement was associated with reduced event-free survival for aneurysm rupture or repair ( P =0.0275), all-cause mortality ( P =0.0635), and aneurysm-related mortality ( P =0.0590). Baseline abdominal aortic aneurysm diameter ( P .0001) and current smoking habit ( P =0.0446) also predicted the primary outcome, and the addition of USPIO enhancement to the multivariate model did not improve event prediction (c-statistic, 0.7935–0.7936). USPIO-enhanced MRI is a novel approach to the identification of aortic wall cellular inflammation in patients with abdominal aortic aneurysms and predicts the rate of aneurysm growth and clinical outcome. However, it does not provide independent prediction of aneurysm expansion or clinical outcomes in a model incorporating known clinical risk factors. URL: www.isrctn.com . Unique identifier: ISRCTN76413758.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 28-02-2020
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 24-05-2013
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.OPHTHA.2019.08.015
Abstract: To describe and compare associations with macular retinal nerve fiber layer (mRNFL), ganglion cell complex (GCC), and ganglion cell-inner plexiform layer (GCIPL) thicknesses in a large cohort. Cross-sectional study. We included 42 044 participants in the UK Biobank. The mean age was 56 years. Spectral-domain OCT macular images were segmented and analyzed. Corneal-compensated intraocular pressure (IOPcc) was measured with the Ocular Response Analyzer (Reichert, Corp., Buffalo, NY). Multivariable linear regression was used to examine associations with mean mRNFL, GCC, and GCIPL thicknesses. Factors examined were age, sex, ethnicity, height, body mass index (BMI), smoking status, alcohol intake, Townsend deprivation index, education level, diabetes status, spherical equivalent, and IOPcc. Thicknesses of mRNFL, GCC, and GCIPL. We identified several novel independent associations with thinner inner retinal thickness. Thinner inner retina was associated with alcohol intake (most significant for GCIPL: -0.46 μm for daily or almost daily intake compared with special occasion only or never [95% confidence interval (CI), 0.61-0.30] P = 1.1×10 The novel associations we identified may be important to consider when using inner retinal parameters as a diagnostic tool. Associations generally were strongest with GCIPL, particularly for IOP. This suggests that GCIPL may be the superior inner retinal biomarker for macular pathophysiologic processes and especially for glaucoma.
Publisher: BMJ
Date: 19-08-2017
DOI: 10.1136/BJOPHTHALMOL-2017-310526
Abstract: Reticular pseudodrusen (RPD) are a risk factor for late age-related macular degeneration (AMD). Associations between RPD and coronary artery disease (CAD) have been reported from small case–control studies. This study investigated the association of RPD within a predominantly CAD cohort. A subgroup of subjects from a multicentre randomised controlled trial of CT coronary angiography (CTCA) underwent ultrawide field (UWF) retinal imaging CAD determined by CTCA and was categorised as normal, non-obstructive or obstructive. Specific AMD features in UWF images were graded. Standardised grids were used to record the spatial location of AMD features, including RPD. Multivariate confounder adjusted regression models assessed the association between RPD and CAD. The 534 participants were aged 27–75 years (mean 58±9 years 425 (80%) ≥50 years) with a male preponderance (56%). Within the study s le, 178 (33%) had no CAD, 351 (66%) had CAD. RPD was detected in 30 participants (5.6%) and bilaterally in 23. Most participants with bilateral RPD had intermediate AMD 17 (74%). After adjustment for potential confounders (age, sex, drusen µm, smoking status), multivariate analysis found no significant association between CAD and RPD (OR 1.31 95% CI (0.57 to 3.01) p=0.52). A significant association was identified between RPD and intermediate AMD (OR 3.18 95% CI (1.61 to 6.27) p=0.001). We found no evidence to support an association between CAD and RPD. RPD was strongly associated with intermediate AMD features. NCT01149590, Post results.
Publisher: Springer Science and Business Media LLC
Date: 30-09-2014
Publisher: Springer Science and Business Media LLC
Date: 14-08-2017
Publisher: BMJ
Date: 02-2019
DOI: 10.1136/BMJOPEN-2018-025077
Abstract: To describe the rationale, methods and research potential of eye and vision measures available in UK Biobank. UK Biobank is a large, multisite, prospective cohort study. Extensive lifestyle and health questionnaires, a range of physical measures and collection of biological specimens are collected. The scope of UK Biobank was extended midway through data collection to include assessments of other measures of health, including eyes and vision. The eye assessment at baseline included questionnaires detailing past ophthalmic and family history, measurement of visual acuity, refractive error and keratometry, intraocular pressure (IOP), corneal biomechanics, spectral domain optical coherence tomography (OCT) of the macula and a disc–macula fundus photograph. Since recruitment, UK Biobank has collected accelerometer data and begun multimodal imaging data (including brain, heart and abdominal MRI) in 100 000 participants. Dense genotypic data and a panel of 20 biochemistry measures are available, and linkage to medical health records for the full cohort has begun. A total of 502 665 people aged between 40 and 69 were recruited to participate in UK Biobank. Of these, 117 175 took part in baseline assessment of vision, IOP, refraction and keratometry. A subgroup of 67 321 underwent OCT and retinal photography. The introduction of eye and vision measures in UK Biobank was accompanied by intensive training, support and a data monitoring quality control process. UK Biobank is one of the largest prospective cohorts worldwide with extensive data on ophthalmic diseases and conditions. Data collection is an ongoing process and a repeat of the baseline assessment including the questionnaires, measurements and s le collection will be performed in subsets of 25 000 participants every 2–3 years. The depth and breadth of this dataset, coupled with its open-access policy, will create a powerful resource for all researchers to investigate the eye diseases in later life.
Publisher: Elsevier BV
Date: 07-2023
Publisher: Public Library of Science (PLoS)
Date: 22-05-2015
Publisher: Springer Science and Business Media LLC
Date: 27-11-2019
DOI: 10.1038/S42003-019-0634-9
Abstract: A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG) intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is h ered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH.
Publisher: Springer Science and Business Media LLC
Date: 03-11-2022
DOI: 10.1038/S41433-022-02298-7
Abstract: This study aims to describe the grading methods and baseline characteristics for UK Biobank (UKBB) participants who underwent retinal imaging in 2009–2010, and to characterise in iduals with retinal features suggestive of age-related macular degeneration (AMD), glaucoma and retinopathy. Non-mydriatic colour fundus photographs and macular optical coherence tomography (OCT) scans were manually graded by Central Administrative Research Facility certified graders and quality assured by clinicians of the Network of Ophthalmic Reading Centres UK. Captured retinal features included those associated with AMD (≥1 drusen, pigmentary changes, geographic atrophy or exudative AMD either imaging modality), glaucoma (≥0.7 cup-disc ratio, ≥0.2 cup-disc ratio difference between eyes, other abnormal disc features photographs only) and retinopathy (characteristic features of diabetic retinopathy with or without microaneurysms either imaging modality). Suspected cases of these conditions were characterised with reference to diagnostic records, physical and biochemical measurements. Among 68,514 UKBB participants who underwent retinal imaging, the mean age was 57.3 years (standard deviation 8.2), 45.7% were men and 90.6% were of White ethnicity. A total of 64,367 participants had gradable colour fundus photographs and 68,281 had gradable OCT scans in at least one eye. Retinal features suggestive of AMD and glaucoma were identified in 15,176 and 2184 participants, of whom 125 (0.8%) and 188 (8.6%), respectively, had a recorded diagnosis. Of 264 participants identified to have retinopathy with microaneurysms, 251 (95.1%) had either diabetes or hypertension. This dataset represents a valuable addition to what is currently available in UKBB, providing important insights to both ocular and systemic health.
Publisher: American Society of Mechanical Engineers
Date: 20-06-2012
Abstract: Abdominal aortic aneurysms (AAAs) remain a significant cause of death in the Western world with over 15,000 deaths per year in the US linked to AAA rupture. There is a general belief among the clinical and engineering community that improved methods of risk prediction are needed. The growth and expansion of AAAs over time is thought to be associated with the mechanobiological interactions within the diseased AAA wall. The stresses and strains induced in the wall by the internal blood pressure trigger increased protease activity and turnover of the extracellular matrix (ECM), thus enabling degradation and expansion of the wall. Inflammatory cells also control collagen synthesis and inflammation can reduce the tensile strength of the wall, thus contributing to the likelihood of rupture. Recently, important work by Richards et al. [1] showed that AAAs with specific sites of focal inflammation have threefold higher growth rates than AAAs with non-specific inflammation.
Publisher: Springer Science and Business Media LLC
Date: 28-05-2018
Publisher: Elsevier BV
Date: 05-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2019
Publisher: Springer Science and Business Media LLC
Date: 05-01-2023
Publisher: Elsevier BV
Date: 2006
DOI: 10.1016/J.PRETEYERES.2005.07.001
Abstract: As digital imaging and computing power increasingly develop, so too does the potential to use these technologies in ophthalmology. Image processing, analysis and computer vision techniques are increasing in prominence in all fields of medical science, and are especially pertinent to modern ophthalmology, as it is heavily dependent on visually oriented signs. The retinal microvasculature is unique in that it is the only part of the human circulation that can be directly visualised non-invasively in vivo, readily photographed and subject to digital image analysis. Exciting developments in image processing relevant to ophthalmology over the past 15 years includes the progress being made towards developing automated diagnostic systems for conditions, such as diabetic retinopathy, age-related macular degeneration and retinopathy of prematurity. These diagnostic systems offer the potential to be used in large-scale screening programs, with the potential for significant resource savings, as well as being free from observer bias and fatigue. In addition, quantitative measurements of retinal vascular topography using digital image analysis from retinal photography have been used as research tools to better understand the relationship between the retinal microvasculature and cardiovascular disease. Furthermore, advances in electronic media transmission increase the relevance of using image processing in 'teleophthalmology' as an aid in clinical decision-making, with particular relevance to large rural-based communities. In this review, we outline the principles upon which retinal digital image analysis is based. We discuss current techniques used to automatically detect landmark features of the fundus, such as the optic disc, fovea and blood vessels. We review the use of image analysis in the automated diagnosis of pathology (with particular reference to diabetic retinopathy). We also review its role in defining and performing quantitative measurements of vascular topography, how these entities are based on 'optimisation' principles and how they have helped to describe the relationship between systemic cardiovascular disease and retinal vascular changes. We also review the potential future use of fundal image analysis in telemedicine.
Publisher: Springer Science and Business Media LLC
Date: 19-03-2020
DOI: 10.1038/S42003-020-0802-Y
Abstract: Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 in iduals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11 / FBLN2 rs2630445, RBP3 rs11204213) others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.
Publisher: Springer Science and Business Media LLC
Date: 24-02-2021
DOI: 10.1038/S41467-020-20851-4
Abstract: Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638 , CLIC5, SLC2A12, YAP1, MXRA5 , and SMAD6 . Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Tom MacGillivray.