Publications by authors named "David Mackey"
Article Synopsis
- Genetic information is becoming more integrated into eye care, especially for conditions like retinoblastoma that stem from single gene mutations, while most eye diseases involve multiple genetic variants and environmental influences.
- The article introduces three genetic epidemiology methods for studying complex eye diseases: genome-wide association studies (GWAS), Polygenic Risk Scores (PRS), and Mendelian randomisation (MR).
- GWAS identifies associations between traits and numerous genetic variants, PRS quantifies an individual's genetic risk based on GWAS findings, and MR examines potential causal relationships between traits using genetic variants as proxies.
Importance: Early detection of glaucoma is essential to timely monitoring and treatment, and primary open-angle glaucoma risk can be assessed by measuring intraocular pressure (IOP) or optic nerve head vertical cup-disc ratio (VCDR). Polygenic risk scores (PRSs) could provide a link between genetic effects estimated from genome-wide association studies (GWASs) and clinical applications to provide estimates of an individual's genetic risk by combining many identified variants into a score.
Objective: To construct IOP and VCDR PRSs with clinically relevant predictive power.
Article Synopsis
- * A multi-ethnic meta-analysis revealed 22 risk loci linked to NTG, with 17 of these not previously identified, including significant new associations with BMP4 and TBKBP1.
- * Findings suggest there’s a genetic overlap in risk factors between NTG and HTG, but NTG shows a generally lower risk effect, pointing to the potential for immunomodulatory treatments as neuroprotective options for glaucoma.
Article Synopsis
- This study aimed to create and validate a polygenic risk score (PRS) for keratoconus to improve how well we can identify people at higher risk for the condition, which can lead to serious vision problems after procedures like LASIK.
- Researchers used multi-trait analysis and data from large biobanks to build and assess the PRS models' accuracy in predicting keratoconus risk.
- The results showed that the new PRS models significantly improved the prediction of keratoconus risk, suggesting they could be useful in clinical settings to identify individuals at risk and potentially prevent complications after LASIK surgery.
Article Synopsis
- * Researchers developed a deep-learning algorithm using over 18,000 fundus images from 20 global databases to accurately screen for glaucoma, comparing its performance using various metrics like sensitivity, specificity, and accuracy.
- * The best-performing model achieved excellent results, with an AUROC of 0.9920, indicating strong ability to differentiate between healthy and glaucomatous images, and also showed solid performance on an external validation dataset.
Age-related cataracts is a highly prevalent eye disorder that results in the clouding of the crystalline lens and is one of the leading causes of visual impairment and blindness. The disease is influenced by multiple factors including genetics, prolonged exposure to ultraviolet radiation, and a history of diabetes. However, the extent to which each of these factors contributes to the development of cataracts remains unclear.
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- Mitochondrial donation is now legally allowed in Australia to help prevent the passing of mitochondrial diseases from mothers to their children as part of a clinical trial.
- A systematic literature review analyzed five cohort studies and 19 case reports on how mitochondrial disease affects pregnancy.
- While many women with mitochondrial disease experience no negative health effects during pregnancy, there is a risk of serious complications, leading to proposed guidelines for preconception counseling and antenatal care.
Purpose: Twin studies, in the background of lack of twin registry in India, are a challenge. We report the response rates in tracing a hospital birth register-based cohort of twins using mail and door to door survey, ocular parameters influencing refractive errors, and their heritability.
Methods: Twins born from 1991 to 1995 in a tertiary hospital in the Vellore District of South India from a database were traced by mail and home survey from March 2011 to September 2013.
Prcis: As additional glaucoma genes are identified and classified, polygenic risk scores will be refined, facilitating early diagnosis and treatment. Ensuring genetic research is equitable to prevent glaucoma blindness worldwide is crucial.
Purpose: To review the progress in glaucoma genetics over the past 25 years, including the identification of genes with varying contributions to the disease and the development of polygenic risk scores.
Purpose: Few studies have explored choroidal changes after cessation of myopia control. This study evaluated the choroidal thickness (ChT) and choroidal vascularity index (CVI) during and after discontinuing long-term low-concentration atropine eye drops use for myopia control.
Methods: Children with progressive myopia (6-16 years; n = 153) were randomized to receive 0.
Article Synopsis
- Optical coherence tomography (OCT) is used to analyze retinal layer thickness and has revealed decreased retinal nerve fiber layer and ganglion cell integrity in Parkinson's disease (PD) patients.
- The study involved young adults undergoing OCT imaging, with genetic risk factors for PD assessed through polygenic risk scores and evaluations of changes in retinal thickness.
- Results indicated a significant link between PD risk scores and macular retinal thickness changes, identifying 27 genes associated with both PD and retinal integrity, suggesting potential causal relationships.
Article Synopsis
- The study aimed to create and validate a deep learning algorithm to automatically assess the cup-to-disc ratio (CDR) from fundus images, as manual assessment can be less reliable and time-intensive.
- A convolutional neural network (CNN) model was trained using over 181,000 fundus images from various databases, demonstrating high accuracy and precision in both image gradability and CDR estimation.
- The algorithm showed promising validation results, achieving an accuracy of up to 99.20% in classification metrics and an impressive coefficient of determination of 0.8514 for CDR estimation, indicating its potential for improving glaucoma screening processes.
This study explored the impact of short-term coronavirus disease 2019 (COVID-19) restrictions on the efficacy of atropine 0.01% eyedrops on myopia control in a multiethnic cohort of Australian children. In the Western Australia Atropine for the Treatment of Myopia study, 104 and 49 children were randomized to receive atropine 0.
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- Deep learning models can learn complex features related to glaucoma, but require extensive data sets; this research focused on creating synthetic optic disc images using diverse data.
- The study utilized 17,060 fundus images to train deep convolutional generative adversarial networks (DCGANs) and evaluated two different models for glaucoma detection: one using only synthetic images and another using a mix of synthetic and real images.
- Results showed that while synthetic images were effective, models trained on a mixed dataset significantly improved performance, achieving a high area under the curve for glaucoma detection, emphasizing the importance of combining synthetic and real clinical data.
Purpose: This study evaluates the performance of a multitrait polygenic risk score (PRS) in an independent cohort to predict incident or progression of keratoconus.
Design: Prospective cross-sectional and cohort study METHODS: Setting: Single-center; Study population: 1478 community-based young adults (18-30 years; 51% female), including 609 (52% female) who returned for an 8-year follow-up; Observation procedures: Scheimpflug imaging (Pentacam, Oculus), genotyping and development of a multitrait PRS previously validated to predict keratoconus in older adults.; Main outcome measure: Belin/Ambrόsio enhanced ectasia display (BAD-D) score and keratoconus, defined as BAD-D ≥2.
Purpose: Genome-wide association studies have recently uncovered many loci associated with variation in intraocular pressure (IOP). Artificial intelligence (AI) can be used to interrogate the effect of specific genetic knockouts on the morphology of trabecular meshwork cells (TMCs) and thus, IOP regulation.
Design: Experimental study.
This study evaluated patient experiences with genetic testing for inherited retinal diseases (IRDs) and the association between underlying knowledge, testing outcomes, and the perceived value of the results. An online survey was distributed to adults with IRDs and parents/guardians of dependents with IRDs who had had genetic testing. Data included details of genetic testing, pre- and post- test perceptions, Decision Regret Scale, perceived value of results, and knowledge of gene therapy.
View Article and Find Full Text PDFMyopia progression following 0.01% atropine cessation in Australian children: Findings from the Western Australia - Atropine for the Treatment of Myopia (WA-ATOM) study.
Clin Exp Ophthalmol
July 2024
Background: A rebound in myopia progression following cessation of atropine eyedrops has been reported, yet there is limited data on the effects of stopping 0.01% atropine compared to placebo control. This study tested the hypothesis that there is minimal rebound myopia progression after cessation of 0.
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- Primary open angle glaucoma (POAG) is a major global cause of blindness, linked to the degeneration of retinal cells, with raised intraocular pressure (IOP) being a significant risk factor.
- The study involved knocking out 62 genes in human trabecular meshwork cells and used advanced techniques like single-cell RNA sequencing and fluorescence analysis to investigate changes in gene expression and cell morphology.
- Results highlighted key genes (ANGPTL2, LMX1B, CAV1, KREMEN1) affecting POAG, revealing potential genetic networks and cellular changes that could help understand the disease's pathogenesis and explore similar genetic disorders.
Although the blinding eye disease glaucoma is more common in people of African ancestry, previous genetic studies predominantly involved European subjects. In this issue of Cell, O'Brien et al. report a genome-wide association study for glaucoma in individuals of African ancestry, showing overlap with European studies and refining an African polygenic risk score.
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- - This study explores how growth patterns during puberty relate to future health outcomes by analyzing height data from about 56,000 individuals across various ancestries using a technique called SITAR.
- - The researchers identified 26 significant genetic loci linked to height growth during puberty and found that different growth rates are associated with various health risks, like type 2 diabetes and heart conditions.
- - The findings suggest that there are multiple growth trajectories during puberty, each influencing adult health differently, indicating that no single growth pattern is the "best" for lifelong health outcomes.
The plant extracellular space, referred to as the apoplast, is inhabited by a variety of microorganisms. Reflecting the crucial nature of this compartment, both plants and microorganisms seek to control, exploit and respond to its composition. Upon sensing the apoplastic environment, pathogens activate virulence programmes, including the delivery of effectors with well-established roles in suppressing plant immunity.
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