Phenotypic consequences of a nanophthalmos-associated TMEM98 variant in human and mouse.

Nanophthalmos is characterised by shorter posterior and anterior segments of the eye, with a predisposition towards high hyperopia and primary angle-closure glaucoma. Variants in TMEM98 have been associated with autosomal dominant nanophthalmos in multiple kindreds, but definitive evidence for causation has been limited. Here we used CRISPR/Cas9 mutagenesis to recreate the human nanophthalmos-associated TMEM98 p.

A Polygenic Risk Score Predicts Intraocular Pressure Readings Outside Office Hours and Early Morning Spikes as Measured by Home Tonometry.

Purpose: Intraocular pressure (IOP) elevations may occur in early morning or outside office hours and can be missed during routine in-clinic IOP measurements. Such fluctuations or peaks likely contribute to glaucoma progression. We sought to investigate the relationship between an IOP polygenic risk score (PRS) and short-term IOP profile.

Corneal Stiffness Parameters Are Predictive of Structural and Functional Progression in Glaucoma Suspect Eyes.

Purpose: To investigate corneal stiffness parameters (SPs) as predictors of future progression risk in glaucoma suspect eyes.

Design: Prospective, longitudinal study.

Participants: Three hundred seventy-one eyes from 228 primary open-angle glaucoma suspects, based on optic disc appearance, with normal baseline Humphrey Visual Field (HVF; Carl Zeiss Meditec) results.

The genetic and clinical landscape of nanophthalmos and posterior microphthalmos in an Australian cohort.

Nanophthalmos and posterior microphthalmos are ocular abnormalities in which both eyes are abnormally small, and typically associated with extreme hyperopia. We recruited 40 individuals from 13 kindreds with nanophthalmos or posterior microphthalmos, with 12 probands subjected to exome sequencing. Nine probands (69.

Using Icare HOME tonometry for follow-up of patients with open-angle glaucoma before and after selective laser trabeculoplasty.

Importance: Monitoring the results of selective laser trabeculoplasty (SLT) on intraocular pressure (IOP) using a home rebound tonometry.

Background: To evaluate the role of Icare HOME tonometry in open-angle glaucoma patients being treated with SLT.

Design: A clinic-based prospective case study.

Macular Ganglion Cell-Inner Plexiform Layer Loss Precedes Peripapillary Retinal Nerve Fiber Layer Loss in Glaucoma with Lower Intraocular Pressure.

Purpose: To investigate which clinical measures influence whether an individual demonstrates earliest glaucomatous structural progression on peripapillary retinal nerve fiber layer (pRNFL) or macular ganglion cell-inner plexiform layer (mGCIPL).

Design: Prospective, longitudinal cohort study.

Participants: Two hundred seventy-one eyes from 207 individuals with statistically significant evidence of glaucomatous progression on OCT Guided Progression Analysis (GPA) software were drawn from a total of 1271 eyes from 686 individuals categorized as glaucoma suspect or having early manifest glaucoma undergoing glaucoma surveillance.

Prevalence and type of artefact with spectral domain optical coherence tomography macular ganglion cell imaging in glaucoma surveillance.

Purpose: The ganglion cell analysis (GCA) of the CIRRUSTM HD-OCT (Carl Zeiss, Meditec; Dublin, CA) provides measurement of the macular ganglion cell-inner plexiform layer (GCIPL) thickness. This study determined the frequency of scan artefacts and errors in GCIPL imaging in individuals undergoing HD-OCT surveillance for glaucoma.

Method: A total of 1439 eyes from 721 subjects enrolled in a prospective study assessing predictors of glaucoma progression underwent macular GCIPL imaging with the CIRRUS HD-OCT at recruitment.

DNA methylation at the 9p21 glaucoma susceptibility locus is associated with normal-tension glaucoma.

Purpose: Recent genome-wide association studies reported strong association of genetic variation at the CDKN2B/CDKN2B-AS1 locus on 9p21 with normal-tension glaucoma (NTG) in multiple populations. The mechanism by which this locus causes disease remains to be elucidated. We investigated the association of DNA methylation of CpG islands at this locus with NTG.

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

Importance: Juvenile open-angle glaucoma (JOAG) is a severe neurodegenerative eye disorder in which most of the genetic contribution remains unexplained.

Objective: To assess the prevalence of pathogenic CYP1B1 sequence variants in an Australian cohort of patients with JOAG and severe visual field loss.

Design, Setting, And Participants: For this cohort study, we recruited 160 patients with JOAG classified as advanced (n = 118) and nonadvanced (n = 42) through the Australian and New Zealand Registry of Advanced Glaucoma from January 1, 2007, through April 1, 2014.

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

Purpose: To investigate the presence of TBK1 copy number variations in a large, well-characterized Australian cohort of patients with glaucoma comprising both normal-tension glaucoma and high-tension glaucoma cases.

Design: A retrospective cohort study.

Methods: DNA samples from patients with normal-tension glaucoma and high-tension glaucoma and unaffected controls were screened for TBK1 copy number variations using real-time quantitative polymerase chain reaction.

Mutation in TMEM98 in a large white kindred with autosomal dominant nanophthalmos linked to 17p12-q12.

Importance: Nanophthalmos is a congenital disorder characterized by small eyes, with the main complications being severe hyperopia and angle-closure glaucoma.

Objective: To perform a clinical and genetic investigation of a large white family with autosomal dominant nanophthalmos.

Design, Setting, And Participants: Detailed clinical evaluation and a genome-wide linkage scan was conducted in the family NNO-SA1.

Association of genetic variants with primary angle closure glaucoma in two different populations.

Purpose: A recent large genome-wide association study (GWAS) identified multiple variants associated with primary angle-closure glaucoma (PACG). The present study investigated the role of these variants in two cohorts with PACG recruited from Australia and Nepal.

Method: Patients with PACG and appropriate controls were recruited from eye clinics in Australia (n = 232 cases and n = 288 controls) and Nepal (n = 106 cases and 204 controls).

Association of eNOS polymorphisms with primary angle-closure glaucoma.

Purpose: Recently, several studies have investigated genetic associations between Cytochrome P450 (CYP1B1), Endothelial nitric oxide synthase (eNOS), and Neurotrophin-4 (NTF4) with primary angle-closure glaucoma (PACG) in various ethnic groups. We investigated the association of these candidate genes with PACG in samples from Australia and Nepal.

Methods: A total of 235 patients with PACG (106 Nepalese and 129 Australian) and 492 controls (204 Nepalese and 288 Australian) was included.

A cross-ethnicity investigation of genes previously implicated in primary angle closure glaucoma.

Purpose: To investigate the underlying genetic variation between candidate genes and primary angle closure glaucoma (PACG) in both Nepalese and Australian populations.

Methods: A total of 213 patients with PACG (106 Nepalese and 107 Australian) and 492 age and sex matched controls (204 Nepalese and 288 Australian) were included in the current study. Three candidate genes were selected; methyl-tetrahydrofolate reductase (MTHFR), calcitonin receptor-like receptor gene (CALCRL), and membrane frizzled-related protein (MFRP).

The association of hepatocyte growth factor (HGF) gene with primary angle closure glaucoma in the Nepalese population.

Purpose: Genetic variation in the hepatocyte growth factor (HGF) gene has recently been associated with hyperopia, which is a known risk factor for primary angle closure glaucoma (PACG). This study aimed to investigate whether genetic variation in HGF is associated with primary angle closure glaucoma in the Nepalese population.

Methods: One hundred six Nepalese patients with primary angle closure glaucoma and 204 matched controls were recruited.

Matrix metalloproteinase-9 genetic variation and primary angle closure glaucoma in a Caucasian population.

Purpose: To investigate the association between genetic variation at the matrix metalloproteinase-9 (MMP9) locus and primary angle closure glaucoma (PACG) in an Australian Caucasian population.

Methods: A total of 107 Australian patients with PACG and 288 age and sex-matched controls were included in the current study. Tag single nucleotide polymorphisms (SNPs) were selected and genotyped to cover the majority of common variation within MMP9.