Clinical Trials

The objective of this study is to evaluate the accuracy and speed of trainees and experienced glaucoma specialists using the MatchedFlicker software against the manual examination of stereoscopic disc photographs for detecting glaucomatous optic disc change. Read More on PubMed

The kernel association test (KAT) is popular in biological studies for its ability to combine weak effects potentially of opposite direction. Its P-value is typically assessed via its (unconditional) asymptotic distribution. However, such an asymptotic distribution is known only for continuous traits and for dichotomous traits. Furthermore, the derived P-values are known to be conservative when sample size is small, especially for the important case of dichotomous traits. One alternative is the permutation test, a widely accepted approximation to the exact finite sample conditional inference. But it is time-consuming to use in practice due to stringent significance criteria commonly seen in these analyses. Read More on PubMed

The burden test and the sequence kernel association test (SKAT) are two popular methods for detecting association with rare variants. Treated as two different sources of association information, they are adaptively combined to form an optimal SKAT (SKAT-O) method for optimal power. We show that the burden test is part of rather than independent of the SKAT. We introduce a new test statistic that is the sum of the burden statistic and a statistic asymptotically independent of the burden statistic. The performance of this new test statistic is demonstrated through extensive simulation studies and applications to a Genetic Analysis Workshop 17 data set and the Ocular Hypertension Treatment Study data. Read More on PubMed

Estimating correlation coefficients among outcomes is one of the most important analytical tasks in epidemiological and clinical research. Availability of multivariate longitudinal data presents a unique opportunity to assess joint evolution of outcomes over time. Bivariate linear mixed model (BLMM) provides a versatile tool with regard to assessing correlation. However, BLMMs often assume that all individuals are drawn from a single homogenous population where the individual trajectories are distributed smoothly around population average. Read More on PubMed

To determine the cumulative incidence of optic disc hemorrhage (ODH) before and after development of primary open-angle glaucoma (POAG); determine the prognostic significance of ODH for the development of POAG; and identify predictive factors for ODH. Read More on PubMed

Primary open-angle glaucoma (POAG) is a major cause of blindness and visual disability. Several genetic risk factors for POAG and optic nerve features have been identified. We measured the relative risk for glaucoma that these factors contribute to participants in the Ocular Hypertension Treatment Study (OHTS). Read More on PubMed

Recent studies indicate that mitochondrial proteins may contribute to the pathogenesis of primary open-angle glaucoma (POAG). In this study, we examined the association between POAG and common variations in gene-encoding mitochondrial proteins. Read More on PubMed

To compare the accuracy and speed of using the computerized MatchedFlicker software program (EyeIC Inc, Narberth, Pennsylvania, USA) to evaluate glaucomatous optic disc change against the traditional gold standard of manually examining stereoscopic disc photographs. Read More on PubMed

Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. To identify new susceptibility loci, we performed meta-analysis on genome-wide association study (GWAS) results from eight independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significantly associated SNPs in two Australian studies (1,252 cases and 2,592 controls), three European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of the top SNPs identified three new associated loci: rs35934224[T] in TXNRD2 (odds ratio (OR) = 0.78, P = 4.05 × 10(-11)) encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] in ATXN2 (OR = 1.17, P = 8.73 × 10(-10)); and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76 × 10(-10)). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest new targets for preventative therapies. Read More on PubMed

To identify objective, quantitative optic nerve head (ONH) structural features and model the contributions of glaucoma. Read More on PubMed

To explore the association between peripapillary atrophy (PPA) area and conversion from ocular hypertension (OHT) to glaucoma. Read More on PubMed

To compare rates of topographic change in ocular hypertensive eyes that develop primary open-angle glaucoma (POAG) compared to eyes that do not, and to identify factors that influence the rate of change. Read More on PubMed

Longitudinal testing plays a key role in glaucoma management. Variability between visits hampers the ability to monitor progression. It has previously been shown that average intraocular pressure (IOP) exhibits seasonal fluctuations. This study examines whether visual field sensitivity also exhibits seasonal fluctuations and seeks to determine whether such fluctuations are correlated to seasonal IOP effects. Read More on PubMed

Trend analysis techniques to detect glaucomatous progression typically assume a constant rate of change. This study uses data from the Ocular Hypertension Treatment Study to assess whether this assumption decreases sensitivity to changes in progression rate, by including earlier periods of stability. Read More on PubMed

To compare rates of visual field (VF) change in ocular hypertensive eyes with and without optic dischemorrhage (DH). Read More on PubMed

To determine the change in intraocular pressure (IOP) after cataract extraction in the observation group of the Ocular Hypertension Treatment Study. Read More on PubMed

To create and validate a statistical model predicting progression of primary open-angle glaucoma (POAG) assessed by loss of visual field as measured in mean deviation (MD) using 3 landmark studies of glaucoma progression and treatment. Read More on PubMed

The goal in this study was to compare rates of visual field (VF) change before and after the initiation of treatment in participants originally randomized to the observation arm of the Ocular Hypertension Treatment Study (OHTS). Read More on PubMed

To determine if the accuracy of the baseline prediction model for the development of primary open-angle glaucoma (POAG) in patients with ocular hypertension can be improved by correcting intraocular pressure (IOP) for central corneal thickness (CCT). Read More on PubMed

To assess the rate of change of visual field (VF) mean deviation (MD) in the Ocular Hypertension Treatment Study (OHTS). Read More on PubMed

Primary open-angle glaucoma (POAG) is among the leading causes of blindness in the United States and worldwide. While numerous prospective clinical trials have convincingly shown that elevated intraocular pressure (IOP) is a leading risk factor for the development of POAG, an increasingly debated issue in recent years is the effect of IOP fluctuation on the risk of developing POAG. In many applications, this question is addressed via a "naïve" two-step approach where some sample-based estimates (e.g., standard deviation) are first obtained as surrogates for the "true" within-subject variability and then included in Cox regression models as covariates. However, estimates from two-step approach are more likely to suffer from the measurement error inherent in sample-based summary statistics. In this paper we propose a joint model to assess the question whether individuals with different levels of IOP variability have different susceptibility to POAG. In our joint model, the trajectory of IOP is described by a linear mixed model that incorporates patient-specific variance, the time to POAG is fit using a semi-parametric or parametric distribution, and the two models are linked via patient-specific random effects. Parameters in the joint model are estimated under Bayesian framework using Markov chain Monte Carlo (MCMC) methods with Gibbs sampling. The method is applied to data from the Ocular Hypertension Treatment Study (OHTS) and the European Glaucoma Prevention Study (EGPS), two large-scale multi-center randomized trials on the prevention of POAG. Read More on PubMed

In some clinical trials and epidemiologic studies, investigators are interested in knowing whether the variability of a biomarker is independently predictive of clinical outcomes. This question is often addressed via a naïve approach where a sample-based estimate (e.g., standard deviation) is calculated as a surrogate for the "true" variability and then used in regression models as a covariate assumed to be free of measurement error. However, it is well known that the measurement error in covariates causes underestimation of the true association. The issue of underestimation can be substantial when the precision is low because of limited number of measures per subject. The joint analysis of survival data and longitudinal data enables one to account for the measurement error in longitudinal data and has received substantial attention in recent years. In this paper we propose a joint model to assess the predictive effect of biomarker variability. The joint model consists of two linked sub-models, a linear mixed model with patient-specific variance for longitudinal data and a full parametric Weibull distribution for survival data, and the association between two models is induced by a latent Gaussian process. Parameters in the joint model are estimated under Bayesian framework and implemented using Markov chain Monte Carlo (MCMC) methods with WinBUGS software. The method is illustrated in the Ocular Hypertension Treatment Study to assess whether the variability of intraocular pressure is an independent risk of primary open-angle glaucoma. The performance of the method is also assessed by simulation studies. Read More on PubMed

To assess agreement between longitudinal and cross-sectional analyses for determining visual field progression in data from the Ocular Hypertension Treatment Study. Read More on PubMed

To determine whether adjusting the intraocular pressure (IOP) change of the trial eye for the IOP change of the fellow eye (i.e., monocular trial) is a better assessment of medication response than testing each eye independently. Read More on PubMed

To evaluate the predictive ability of baseline confocal scanning laser ophthalmoscopy (CSLO) Glaucoma Probability Score (GPS) for the development of primary open-angle glaucoma (POAG) and to compare it with the Moorfields regression analysis (MRA) classification, other topographic optic disc parameters, and stereophotograph-based cup-to-disc ratio. Read More on PubMed

To assess the influence of expected life span on the cost-effectiveness of treating ocular hypertension to prevent primary open-angle glaucoma. Read More on PubMed

To determine the incidence of retinal vein occlusion (RVO) in the Ocular Hypertension Treatment Study (OHTS). Read More on PubMed

To describe variability of intraocular pressure (IOP) measurements within the same eye and between right and left eyes over a 60-month period in participants in the Ocular Hypertension Treatment Study. Read More on PubMed

This report compares the accuracy of 3 prediction models for the development of primary open-angle glaucoma (POAG). The models differ primarily in their handling of these eye-specific variables: intraocular pressure (IOP), central corneal thickness (CCT), vertical cup-to-disc ratio (VCD), and visual field pattern standard deviation (PSD). The "means" model includes age and the means of right and left eyes; the "means plus asymmetry" model includes age, the means of right and left eyes as well as the absolute difference between eyes for eye-specific variables; and the "worse" eye model includes age and values from the eye at higher risk for developing POAG. Read More on PubMed

To describe how much change, if any, occurs between central corneal thickness (CCT) measurements performed an average of 3.8 years apart in participants in the Ocular Hypertension Treatment Study (OHTS) and to identify clinical and demographic factors that are associated with changes in CCT, including baseline intraocular pressure, duration and class of ocular hypotensive medication, medical history, and systemic medication. Read More on PubMed

To report the impact of visual field quality control (QC) procedures on the rates of visual field unreliability, test parameter errors, and visual field defects attributed to testing artifacts in the Ocular Hypertension Treatment Study (OHTS). Read More on PubMed

To compare the intraocular pressure (IOP) responses of self-identified African American and white participants in the Ocular Hypertension Treatment Study to therapeutic trials of topical, nonselective beta-adrenergic antagonists or prostaglandin analogues. Read More on PubMed

To test the validity and generalizability of the Ocular Hypertension Treatment Study (OHTS) prediction model for the development of primary open-angle glaucoma (POAG) in a large independent sample of untreated ocular hypertensive individuals and to develop a quantitative calculator to estimate the 5-year risk that an individual with ocular hypertension will develop POAG. Read More on PubMed

To compare the rates of detection of optic disc hemorrhages by clinical examination and by review of optic disc photographs at the Optic Disc Reading Center (ODRC), to assess the incidence of and the predictive factors for disc hemorrhages in the annual disc photographs of the Ocular Hypertension Treatment Study (OHTS), and to determine whether optic disc hemorrhages predict the development of primary open-angle glaucoma (POAG) in the OHTS. Read More on PubMed

To determine whether topical ocular hypotensive medication is associated with refractive changes, visual symptoms, decreased visual function, or increased lens opacification. Read More on PubMed

To compare subbasal corneal nerve and keratocyte density and endothelial characteristics of ocular hypertensive patients treated with medications or observation. Read More on PubMed

To evaluate whether baseline visual field data and asymmetries between eyes predict the onset of primary open-angle glaucoma (POAG) in Ocular Hypertension Treatment Study (OHTS) participants. Read More on PubMed

To determine the association between change from baseline in the optic nerve head (ONH) and the visual field (VF) during follow-up of ocular hypertension participants in the Ocular Hypertension Treatment Study. Read More on PubMed

The Ocular Hypertension Treatment Study (OHTS) demonstrated that medical treatment of people with intraocular pressure (IOP) of > or =24 mm Hg reduces the risk of the development of primary open-angle glaucoma (POAG) by 60%. There is no consensus on which people with ocular hypertension would benefit from treatment. Read More on PubMed

To assess the reproducibility of determining whether an eye has developed optic disk deterioration by the Optic Disc Reading Center (ODRC) in the Ocular Hypertension Treatment Study (OHTS). Read More on PubMed

To determine whether baseline confocal scanning laser ophthalmoscopy (CSLO) optic disc topographic measurements are associated with the development of primary open-angle glaucoma (POAG) in individuals with ocular hypertension. Read More on PubMed

To compare the occurrence of normal visual field (VF) test results following 2 vs 3 consecutive, abnormal, reliable test results in the Ocular Hypertension Treatment Study. Read More on PubMed

To determine whether central corneal thickness (CCT) correlates with measured intraocular pressure (IOP) response to topical ocular hypotensive medication in the Ocular Hypertension Treatment Study (OHTS). Read More on PubMed

Higher baseline pattern standard deviation (PSD) and larger vertical cup-to-disk ratio (VC/D) were factors in the predictive model for the development of primary open-angle glaucoma (POAG) in the Ocular Hypertension Treatment Study. Because early changes in PSD and VC/D may be indicative of early POAG damage, we repeated the prediction model excluding PSD and VC/D. Read More on PubMed

The prevalence of glaucoma is higher in African American individuals than in white individuals. Read More on PubMed

To describe the study design of the Confocal Scanning Laser Ophthalmoscopy (CSLO) Ancillary Study to the Ocular Hypertension Treatment Study (OHTS) and to examine the associations between optic disk topography, and baseline demographic, clinical, and ocular factors at study entry. Read More on PubMed

To examine racial differences in optic disc topography among ocular hypertensive participants in the Ocular Hypertension Treatment Study. Read More on PubMed

(1) To develop a classification system for visual field (VF) abnormalities, (2) to determine interreader and test-retest agreement, and (3) to determine the frequency of various VF defects in the Ocular Hypertension Treatment Study. Read More on PubMed

Primary open-angle glaucoma (POAG) is one of the leading causes of blindness in the United States and worldwide. Three to 6 million people in the United States are at increased risk for developing POAG because of elevated intraocular pressure (IOP), or ocular hypertension. There is no consensus on the efficacy of medical treatment in delaying or preventing the onset of POAG in individuals with elevated IOP. Therefore, we designed a randomized clinical trial, the Ocular Hypertension Treatment Study. Read More on PubMed

The Ocular Hypertension Treatment Study (OHTS) has shown that topical ocular hypotensive medication is effective in delaying or preventing the onset of primary open-angle glaucoma (POAG) in individuals with elevated intraocular pressure (ocular hypertension) and no evidence of glaucomatous damage. Read More on PubMed

The Ocular Hypertension Treatment Study (OHTS) seeks to evaluate the safety and efficacy of topical ocular hypotensive medication in preventing or delaying the onset of visual field loss and/or optic nerve damage in ocular hypertensive subjects at risk for developing primary open-angle glaucoma. This study evaluates the baseline visual field test characteristics (visual field status, reliability properties, etc.) of patients who underwent eligibility visual field testing for entry to the OHTS. Read More on PubMed

To determine the reproducibility over time of visual estimates of the horizontal cup/disk ratio by trained technicians from optic disk stereophotographs. Read More on PubMed

Central corneal thickness influences intraocular pressure (IOP) measurement. We examined the central corneal thickness of subjects in the Ocular Hypertension Treatment Study (OHTS) and determined if central corneal thickness is related to race. Read More on PubMed

To evaluate the magnitude of the contralateral effect of topically administered beta-blockers on intraocular pressure. Read More on PubMed

To determine the frequency with which visual field abnormalities observed on follow-up visual fields for patients in the Ocular Hypertension Treatment Study were confirmed on retest. Read More on PubMed

The Ocular Hypertension Treatment Study (OHTS) seeks to evaluate the safety and efficacy of topical ocular hypotensive medication in preventing or delaying the onset of visual field loss and/or optic nerve damage in subjects with ocular hypertension at moderate risk for developing primary open angle glaucoma. Read More on PubMed