David A. Mackey

Current state and future prospects of artificial intelligence in ophthalmology: a review.

Important key terms such as machine learning and deep learning are often misunderstood and incorrectly used interchangeably. This article presents an overview of AI and new developments relevant to ophthalmology.

Association of Genetic Variation With Keratoconus.

In this relatively large keratoconus genome-wide association study, we identified a genome-wide significant locus for keratoconus in the region of PNPLA2 on chromosome 11.

Prevalence of FOXC1 Variants in Individuals With a Suspected Diagnosis of Primary Congenital Glaucoma.

These data highlight the genetic and phenotypic heterogeneity of childhood glaucoma and support the use of gene panels incorporating FOXC1 as a diagnostic aid, especially because clinical features of Axenfeld-Rieger syndrome can be subtle.

Sleep and eye disease: A review.

Reports of ocular surface complications secondary to leaking CPAP masks highlights the importance of ensuring good mask fit.

Biallelic CPAMD8 Variants Are a Frequent Cause of Childhood and Juvenile Open-Angle Glaucoma.

Biallelic CPAMD8 variation was associated with a highly heterogeneous phenotype and in our cohorts was the second most common inherited cause of childhood glaucoma after CYP1B1 and juvenile open-angle glaucoma after MYOC.

Myocilin Gene Gln368Ter Variant Penetrance and Association With Glaucoma in Population-Based and Registry-Based Studies.

The MYOC p.Gln368Ter variant confers a very high-risk effect size for advanced glaucoma; the risk is lower in nonadvanced glaucoma and OHT.

Childhood and Early Onset Glaucoma Classification and Genetic Profile in a Large Australasian Disease Registry.

We report on the largest cohort of individuals with childhood and early onset glaucoma from Australasia using the CGRN classification.

Genome-Wide Meta-analysis Identifies Risk Loci and Improves Disease Prediction of Age-Related Macular Degeneration.

Our findings improve the knowledge of the genetic architecture of AMD and help achieve better accuracy in AMD prediction.

Myocilin Predictive Genetic Testing for Primary Open-Angle Glaucoma Leads to Early Identification of At-Risk Individuals.

Our findings demonstrated that MYOC cascade genetic testing for POAG allows identification of at-risk individuals at an early stage or even before signs of glaucoma are present.

Association of Novel Loci With Keratoconus Susceptibility in a Multitrait Genome-Wide Association Study of the UK Biobank Database and Canadian Longitudinal Study on Aging.

These findings support the use of multitrait modeling of corneal parameters in a relatively large data set to identify new keratoconus risk loci and enhance polygenic risk score models.

Mitochondrial DNA Variation and Disease Susceptibility in Primary Open-Angle Glaucoma.

Mitochondrial DNA ancestral lineages modulate the risk for primary open-angle glaucoma in populations of European descent.

Associations between Optic Disc Measures and Obstructive Sleep Apnea in Young Adults.

Obstructive sleep apnea may be associated with preclinical thinning of the peripapillary RNFL in young adults.

Association of Monogenic and Polygenic Risk With the Prevalence of Open-Angle Glaucoma.

Monogenic and high polygenic risk were each associated with a more than 2.5-fold increased odds of developing glaucoma and an equivalent mean age at glaucoma diagnosis, with high polygenic risk more than 15 times more…

Attitudes Towards Polygenic Risk Testing in Individuals with Glaucoma.

These findings will help to facilitate the clinical implementation of PRS testing for glaucoma to reduce irreversible vision loss.

Genetic Correlations Between Diabetes and Glaucoma: An Analysis of Continuous and Dichotomous Phenotypes.

These analyses suggest that there is limited genetic correlation between diabetes- and glaucoma-related traits.

Testosterone Pathway Genetic Polymorphisms in Relation to Primary Open-Angle Glaucoma: An Analysis in Two Large Datasets.

Collectively, testosterone metabolism pathway SNPs were consistently associated with the high-tension subtype of POAG in two datasets.

Contribution of Mutations in Known Mendelian Glaucoma Genes to Advanced Early-Onset Primary Open-Angle Glaucoma.

Rare, potentially disease-causing variants in Mendelian POAG genes that showed enrichment in our dataset were found in 22.9% of advanced early-onset POAG cases.

Assessing the Efficacy of Synthetic Optic Disc Images for Detecting Glaucomatous Optic Neuropathy Using Deep Learning.

Although our model performed well on synthetic data, training on a mixed data set demonstrated better performance and generalization.

Comparison of Anterior Segment Abnormalities in Individuals With FOXC1 and PITX2 Variants.

Corneal abnormalities were more common in individuals with FOXC1 than in those with PITX2 variants and were often associated with early onset glaucoma.

Optic Disc Measures in Obstructive Sleep Apnea: A Community-based Study of Middle-aged and Older Adults.

Our findings do not provide strong evidence of a link between measures of OSA and the optic disc.

A Multitrait Open-Angle Glaucoma Polygenic Risk Score Stratifies Risk of Glaucoma Diagnosis and Severity in Eyes with Pseudoexfoliation.

The PRSs for open-angle glaucoma, IOP, and VCDR stratify risk of glaucoma development and disease severity among individuals with PEX.

Attitudes Toward Glaucoma Genetic Risk Assessment in Unaffected Individuals.

Our results show strong interest in genetic risk assessment for glaucoma among unaffected individuals in Australia.

Genetic Associations Between Smoking- and Glaucoma-Related Traits.

MR experiments and GRS generated from Rotterdam Study participants support an inverse relationship between smoking and glaucoma.

Do Levels of Stress Markers Influence the Retinal Nerve Fiber Layer Thickness in Young Adults?

Although there was a link between ACTH or adrenal sensitivity and RNFL thickness, this association was weak and its clinical significance is unclear.

A generalised computer vision model for improved glaucoma screening using fundus images.

This study demonstrated the high efficacy of our classification model in distinguishing between glaucomatous and healthy discs.

Is Genetic Risk for Sleep Apnea Causally Linked With Glaucoma Susceptibility?

We found little genetic evidence supporting a causal association between SA and glaucoma.

Association between dietary niacin and retinal nerve fibre layer thickness in healthy eyes of different ages.

Dietary intake of niacin from a standard diet does not appear to be associated with age-related RNFL thinning in healthy eyes. Supraphysiological doses of niacin may be required for therapeutic effect in the retina.

Predictive Power of Polygenic Risk Scores for Intraocular Pressure or Vertical Cup-Disc Ratio.

VCDR and IOP PRSs derived using a large recently published multitrait GWAS exhibited validity across independent cohorts.

Seeing the impact of the Glaucoma Inheritance Study in Tasmania after 25 years.

Polygenic Risk Prediction for Normal-Tension Glaucoma.

Despite the limited sample size of current NTG GWASs, our findings suggest that NTG-specific PRSs hold promise for risk prediction.

Longitudinal Change in Retinal Nerve Fiber Layer Thickness and Intraocular Pressure in Young Adults.

During the third decade of life, there is a decrease in pRNFL thickness and IOP in healthy adults.

Evaluating the effectiveness of cascade clinical screening for familial glaucoma in rural Western Australia.

Physical Activity and Cardiovascular Fitness During Childhood and Adolescence: Association With Retinal Nerve Fibre Layer Thickness in Young Adulthood.

The association between estimated cardiovascular fitness and pRNFL thickness suggests there may be overlapping mechanisms for cardiovascular health and retinal ganglion cell integrity.

Association of Polygenic Scores for Glaucoma With Measures of Retinal Ganglion Cell Integrity in Young and Older Adults.

Associations between PGS and optic disc measures were present from young adulthood, but the effect sizes were greater in older adults.

Evaluating Practical Approaches for Including MYOC Variants Alongside Common Variants for Genetics-Based Risk Stratification for Glaucoma.

The p.Gln368Ter variant can be genotyped with high accuracy using array data, provided careful quality control measures are implemented. Incorporating p.Gln368Ter into glaucoma PRS improved risk stratification for carriers.

Genetic Association at the 9p21 Glaucoma Locus Contributes to Sex Bias in Normal-Tension Glaucoma.

This study demonstrated that female sex is a risk factor for developing advanced NTG.

Inter-device comparison of retinal sensitivity measurements: the CenterVue MAIA and the Nidek MP-1.

The large LoA and variation in scotoma mapping concordance suggest that the same microperimeter should be used for follow-up examination. We recommend caution in comparing results derived from different types of microperimeters.

Accurate Imputation-Based Screening of Gln368Ter Myocilin Variant in Primary Open-Angle Glaucoma.

We demonstrate that some clinically important rare variants can be reliably detected using arrays and imputation.

Occurrence of CYP1B1 Mutations in Juvenile Open-Angle Glaucoma With Advanced Visual Field Loss.

Patients with advanced JOAG based on visual field loss had enrichment of CYP1B1 pathogenic variants and a more severe phenotype compared with unaffected controls and patients with nonadvanced JOAG.

Swimming goggle wear is not associated with an increased prevalence of glaucoma.

These findings suggest that frequently wearing swim goggles does not lead to an increased risk of glaucoma over time in adults.

Copy number variations of TBK1 in Australian patients with primary open-angle glaucoma.

We report the presence of TBK1 copy number variations in our Australian normal-tension glaucoma cohort, including the first example of more than 1 extra copy of this gene in glaucoma patients (gene triplication).