Wiggs Janey L

Intraocular Pressure, Glaucoma, and Dietary Caffeine Consumption: A Gene-Diet Interaction Study from the UK Biobank.

Habitual caffeine consumption was associated weakly with lower IOP, and the association between caffeine consumption and glaucoma was null.

Association of Long-term Ambient Black Carbon Exposure and Oxidative Stress Allelic Variants With Intraocular Pressure in Older Men.

Ambient black carbon exposure may be a risk factor for increased intraocular pressure in individuals susceptible to other biological oxidative stressors.

Association of APOE With Primary Open-Angle Glaucoma Suggests a Protective Effect for APOE ε4.

We have found that the APOE ε4 allele is associated with a reduced risk of POAG.

The genetic basis for adult onset glaucoma: Recent advances and future directions.

We will discuss how recent advances in research methodology have uncovered new risk genes, and how follow up biological investigations could be undertaken in order to define how the risk encoded by a genetic sequence variant comes into play in patients.

Alcohol, Intraocular Pressure, and Open-Angle Glaucoma: A Systematic Review and Meta-analysis.

Although this meta-analysis suggests a harmful association between alcohol use and OAG, our results should be interpreted cautiously given the weakness and heterogeneity of the underlying evidence base, the small absolute effect size, and the borderline statistical significance.

Prospective Study of Oral Health and Risk of Primary Open-Angle Glaucoma in Men: Data from the Health Professionals Follow-up Study.

Although the number of natural teeth was not associated with risk of POAG, recent tooth loss was associated with an increased risk of POAG.

The genetics of glaucoma: Disease associations, personalised risk assessment and therapeutic opportunities-A review.

Here, we summarise the known genetic associations for various forms of glaucoma and the possible functional roles for these genes in disease pathogenesis.

Association of Statin Use and High Serum Cholesterol Levels With Risk of Primary Open-Angle Glaucoma.

Among adults aged 40 years or older, higher serum cholesterol levels were associated with higher risk of POAG, while 5 or more years of statin use compared with never use of statins was associated with…

The Association between Serum Lipids and Intraocular Pressure in 2 Large United Kingdom Cohorts.

Our findings suggest that serum TC, HDL-C, and LDL-C are associated positively with IOP in 2 United Kingdom cohorts and that triglyceride levels may be associated negatively.

The Association of Physical Activity with Glaucoma and Related Traits in the UK Biobank.

Higher overall PA level and greater time spent in moderate and vigorous PA were not associated with glaucoma status but were associated with thicker mGCIPL.

The Association of Alcohol Consumption with Glaucoma and Related Traits: Findings from the UK Biobank.

Alcohol intake was consistently and adversely associated with glaucoma and related traits, and at levels below current United Kingdom (< 112 g/week) and United States (women, < 98 g/week; men, < 196 g/week) guidelines.

Association of a Primary Open-Angle Glaucoma Genetic Risk Score With Earlier Age at Diagnosis.

A higher dose of POAG risk alleles was associated with an earlier age at glaucoma diagnosis.

Deep Ocular Phenotyping Across Primary Open-Angle Glaucoma Genetic Burden.

Results suggest that PRS identified a group of individuals at substantially higher risk for POAG.

Calcium Channel Blocker Use and Associated Glaucoma and Related Traits Among UK Biobank Participants.

In this study, an adverse association between CCB use and glaucoma was observed, with CCB users having, on average, 39% higher odds of glaucoma.

Cohort Study of Race/Ethnicity and Incident Primary Open-Angle Glaucoma Characterized by Autonomously Determined Visual Field Loss Patterns.

Blacks, compared to non-Hispanic whites, had higher risks of POAG with early central and advanced VF loss.

Polygenic Risk Scores for Glaucoma Onset in the Ocular Hypertension Treatment Study.

Higher PRS was associated with increased risk for POAG in patients with ocular hypertension. The inclusion of a PRS improved the prediction of POAG onset.

The Association of Female Reproductive Factors with Glaucoma and Related Traits: A Systematic Review.

The association between PMH use and lower IOP or OAG risk is a potentially clinically relevant and modifiable risk factor and should be investigated further, although this needs to be interpreted in the context of a high risk of bias across included studies.

Myocilin Mutations in Patients With Normal-Tension Glaucoma.

In cohorts 1 and 2, the p.Gln368Ter mutation in MYOC was found in patients with IOPs that were 21 mm Hg or lower (NTG), although at a frequency that is lower than previously detected in patients with higher IOP.

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.

Prospective study of flavonoid intake and risk of primary open-angle glaucoma.

Total flavonoid intake was not associated with POAG risk. Greater intakes of flavonols and monomeric flavanols and of tea showed suggestive modest associations with lower risk; these results need confirmation.

LOXL1 Polymorphisms: Genetic Biomarkers that Presage Environmental Determinants of Exfoliation Syndrome.

Prospective studies have also implicated higher coffee consumption and lower dietary folate intake in association with incident XFS.

The Genetic Influence on Corticosteroid-Induced Ocular Hypertension: A Field Positioned for Discovery.

There is substantial evidence suggesting a genetic component to corticosteroid-related ocular hypertension and glaucoma, but specific genetic risk factors have yet to be identified.

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.

Genome-Wide Association Study Identifies Two Common Loci Associated with Pigment Dispersion Syndrome/Pigmentary Glaucoma and Implicates Myopia in its Development.

Common SNPs relating to the GSAP and GRM5/TYR genes are associated risk factors for the development of PDS and PG.

Development of Primary Open Angle Glaucoma-Like Features in a Rhesus Macaque Colony From Southern China.

Members of a nonhuman primate colony exhibit important ophthalmic features of human primary open-angle glaucoma.

Characteristics of p.Gln368Ter Myocilin Variant and Influence of Polygenic Risk on Glaucoma Penetrance in the UK Biobank.

One in 4 individuals with the MYOC p.Gln368Ter mutation demonstrated evidence of glaucoma, a substantially higher penetrance than previously estimated, with 69% of cases undetected.

A Role for Clusterin in Exfoliation Syndrome and Exfoliation Glaucoma?

Future studies investigating rare CLU variation and other complex interactions including gene-gene interactions in XFS/XFG cases and controls may also be fruitful.

Fundus Densitometry Findings Suggest Optic Disc Hemorrhages in Primary Open-Angle Glaucoma Have an Arterial Origin.

DH have densitometry profiles comparable to MA and different from RVO, suggesting that DH in glaucoma have an arterial origin.

Long-term Alcohol Consumption and Risk of Exfoliation Glaucoma or Glaucoma Suspect Status among United States Health Professionals.

Long-term alcohol consumption was associated with a higher risk of XFG/XFGS status. Our findings provide further clues regarding the XFG/XFGS etiology.

Association of the CAV1-CAV2 locus with normal-tension glaucoma in Chinese and Japanese.

In this study, we confirmed the association of rs4236601 at the CAV1-CAV2 locus with NTG in Chinese.

Cohort Study of Nonmelanoma Skin Cancer and the Risk of Exfoliation Glaucoma.

NMSC was associated with higher XFG risk, particularly among younger participants and those living in the Northern US.

Use of Diagnostic Codes for Primary Open-Angle Glaucoma Polygenic Risk Score Construction in Electronic Health Record-Linked Biobanks.

A POAG PRS performed similarly using either manual review or ICD codes in 2 electronic health record-linked biobanks; manual assessment of glaucoma status might not be necessary for some PRS studies.

Prediagnostic Plasma Metabolomics and the Risk of Exfoliation Glaucoma.

In plasma from a decade before diagnosis, lysophosphatidylcholines and phosphatidylethanolamine plasmalogens were positively associated and triacylglycerols and steroids (e.g., cortisone) were inversely associated with XFG risk.

Statin Use in Relation to Intraocular Pressure, Glaucoma, and Ocular Coherence Tomography Parameters in the UK Biobank.

We found no evidence of a protective association between statin use and glaucoma or related traits after adjusting for key confounders.

CPAMD8, a New Gene for Anterior Segment Dysgenesis and Childhood Glaucoma.

Mitochondrial TXNRD2 and ME3 Genetic Risk Scores Are Associated with Specific Primary Open-Angle Glaucoma Phenotypes.

Patients with POAG with higher TXNRD2 and ME3 GRSs showed higher treated IOP and a greater prevalence of paracentral field loss.

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.

The Clinical Usefulness of a Glaucoma Polygenic Risk Score in 4 Population-Based European Ancestry Cohorts.

Incorporating a PRS into a POAG predictive model improves identification concordance from 0.75 up to 0.82, supporting its potential for guiding more cost-effective screening strategies.

Independent Effects of Blood Pressure on Intraocular Pressure and Retinal Ganglion Cell Degeneration: A Mendelian Randomization Study.

These findings support a causal effect of elevated blood pressure on retinal ganglion cell degeneration that does not require intermediary changes in IOP.

The Association of Urinary Sodium Excretion with Glaucoma and Related Traits in a Large United Kingdom Population.

Urinary sodium excretion, a biomarker of dietary intake, may represent an important modifiable risk factor for glaucoma, especially in individuals at high underlying genetic risk.

The Heritability of Primary Angle Closure Anatomic Traits and Predictors of Angle Closure in South Indian Siblings.

Iris, anterior chamber, and lens parameters may be heritable whereas angle parameters were not.

Primary Open-Angle Glaucoma Polygenic Risk Score and Risk of Disease Onset: A Post Hoc Analysis of a Randomized Clinical Trial.

These findings support considering use of a POAG PRS threshold to identify individuals at low risk of disease onset, with those below the PRS threshold more likely to have lower conversion rates over 20 years.

Prospective study of dietary intake of branched-chain amino acids and the risk of primary open-angle glaucoma.

Higher dietary intake of BCAA was not associated with POAG risk.

Head and Neck Region Dermatological Ultraviolet-Related Cancers are Associated with Exfoliation Syndrome in a Clinic-Based Population.

Head and neck region BCCs or SCCs are associated with a higher risk of having XFS or XFG.

Genetic Associations of Primary Angle-Closure Disease: A Systematic Review and Meta-Analysis.

This study revealed the genetic complexity of primary angle-closure disease, involving common SNVs and rare coding variants in more than 30 genes or loci, with ethnic and phenotypic diversities.

Notice of Retraction and Replacement. Kang et al. Association of statin use and high serum cholesterol levels with risk of primary open-angle glaucoma. JAMA Ophthalmol. 2019;137(7):756-765.

Does Age Modify the Relation Between Genetic Predisposition to Glaucoma and Various Glaucoma Traits in the UK Biobank?

With increasing age, an mtGPRS was a better predictor of higher IOP and glaucoma prevalence. It is useful to consider chronological age with genetic information in designing glaucoma screening strategies.

Childhood or adolescent abuse and primary open-angle glaucoma in a longitudinal cohort of women.

While any childhood/adolescence abuse history was not associated with POAG, the modest adverse associations with early-life sexual abuse history warrant confirmation in future studies.

Glaucoma Genetics: Lessons Learned and the New Frontier.

Priorities for future work include the discovery of novel genes and genetic causality, as well as functional studies to define molecular mechanisms underlying disease pathophysiology.

ChatGPT-Assisted Glaucoma Diagnosis: A Health-Equitable Multi-Ancestry Analysis Using Visual Field and Optical Coherence Tomography Data.

ChatGPT o1 Pro diagnosed glaucoma similarly to specialists using only VF and OCT data. The model performance was similar across ancestral groups and genetic predispositions to glaucoma.

Time-Dependent Glucocorticoid-Induced Transcriptomic Changes in Human Trabecular Meshwork and Schlemm's Canal Cells.

This study identified candidate genes and pathways for glucocorticoid-induced ocular hypertension which can be further explored in human genetic analyses.

Using Genetics for Glaucoma Screening and Risk Stratification: The LXXXII Edward Jackson Memorial Lecture.

Recent advances in glaucoma genetics are providing new opportunities to use genetic information to guide prevention, diagnosis, and treatment of disease and ultimately to develop a personalized approach to glaucoma clinical care.

Dual-Level Pattern Tree for Visual Field Improves Glaucoma Progression and Polygenic Risk Prediction.

Trunk-branch VF classifiers were superior to trunk-only characterizations for predicting functional progression and glaucoma PRS.

Female Reproductive Factors in Relation to Risk of Exfoliation Glaucoma or Glaucoma Suspect.

Later age at menarche was associated with a lower XFG/XFGS risk. Surgical versus natural menopause was inversely associated with XFG/XFGS risk only among those with high genetic susceptibility. These results need confirmation.

Genetic Risk for Open-Angle Glaucoma Subtypes Is Associated with Specific Visual Field Defect Classes.

Higher POAG PRSs and NTG PRSs were associated with paracentral VF loss, whereas higher HTG GRS was linked to total VF loss, but not paracentral defects.

Relationship Between Oral Health and Glaucoma Traits in the United Kingdom.

Self-reported oral health was not associated with elevated IOP or an increased risk of glaucoma. Future studies should confirm the null association between clinically diagnosed oral health conditions and glaucoma.

Exfoliation syndrome: assembling the puzzle pieces.

Meeting participants concluded that it is unclear how the mild homocysteinemia seen in XFS might contribute to the disarrayed extracellular aggregates characteristic of this syndrome.

Assessing the Association of Mitochondrial Genetic Variation With Primary Open-Angle Glaucoma Using Gene-Set Analyses.

We present an effective approach for assessing the contributions of mitochondrial genetic variation to open-angle glaucoma.

A Common Variant in MIR182 Is Associated With Primary Open-Angle Glaucoma in the NEIGHBORHOOD Consortium.

Our integrative study is the first to associate rs76481776 with POAG via elevated miR-182 expression.

Association of Dietary Nitrate Intake With Primary Open-Angle Glaucoma: A Prospective Analysis From the Nurses' Health Study and Health Professionals Follow-up Study.

Higher dietary nitrate and green leafy vegetable intake was associated with a lower POAG risk, particularly POAG with early paracentral VF loss at diagnosis.

Drug-induced Bilateral Secondary Angle-Closure Glaucoma: A Literature Synthesis.

Several compound preparations were implicated in drug-induced bilateral 2° ACG.

Nailfold Capillary Abnormalities in Primary Open-Angle Glaucoma: A Multisite Study.

These data provided support for nonocular capillary bed abnormalities in POAG. Comparable vascular abnormalities in the optic nerve may render it susceptible to glaucomatous damage.

Author Response: Comparison of Risk Factor Profiles for Primary Open-Angle Glaucoma Subtypes Defined by Pattern of Visual Field Loss: True Risk Factors or Arbituary Definition?

Comparison of Risk Factor Profiles for Primary Open-Angle Glaucoma Subtypes Defined by Pattern of Visual Field Loss: A Prospective Study.

These data indicate that POAG with early paracentral VF loss has distinct as well as common determinants compared with POAG with peripheral VF loss.