Validated Prediction Model for the Development of Primary Open-Angle Glaucoma in Individuals with Ocular Hypertension

Abstract

Objective-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. To develop a quantitative calculator to estimate the 5-year risk that an individual with ocular hypertension will develop POAG.Design-A prediction model was developed from the observation group of the OHTS and then tested on the placebo group of the European Glaucoma Prevention Study (EGPS) using a z-statistic to compare hazard ratios, a c-statistic for discrimination and a calibration chi-square for systematic over/under estimation of predicted risk. The two study samples were pooled to increase precision and generalizability of a 5-year predictive model for developing POAG.Participants-The OHTS observation group (n=819, 6.6 years median follow-up) and the EGPS placebo group (n=500, 4.8 years median follow-up).Testing-Data were collected on demographic characteristics, medical history, ocular examination visual fields and optic disc photographs.Main Outcome Measures-Development of reproducible visual field abnormality or optic disc progression as determined by masked readers and attributed to POAG by a masked endpoint committee.Results-The same predictors for the development of POAG were independently identified in both the OHTS observation group and the EGPS placebo group -baseline age, intraocular pressure (IOP), central corneal thickness, vertical cup/disc ratio, and Humphrey visual field pattern standard deviation. The pooled multivariate model for the development of POAG had good discrimination (cstatistic 0.74) and accurate estimation of POAG risk (calibration chi-square 7.05). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptOphthalmology. Author manuscript; available in PMC 2008 January 1. Conclusions-The OHTS prediction model was validated in the EGPS placebo group. A calculator to estimate the 5-year risk of developing POAG, based on the pooled OHTS-EGPS predictive model, has high precision and will be useful to clinicians and patients in deciding the frequency of tests and examinations during follow-up and the advisability of initiating preventive treatment.

Predicting Development of Glaucomatous Visual Field Conversion Using Baseline Fourier-Domain Optical Coherence Tomography

“…The most established risk calculator is based on data from the OHTS and the European Glaucoma Prevention study. 3 It includes the IOP, CCT, age, CDR, and VF PSD. The OHTS-derived model has been tested in an independent study population.…”

“…Several studies have tried to identify and combine anatomic, visual field (VF) and epidemiological variables to create a risk calculator. Investigators in the Ocular Hypertension Treatment Study (OHTS) 1 and in OHTS validation studies 2,3 developed a formula that tries to predict the onset of primary open angle glaucoma (POAG) using a number of standard glaucoma variables: IOP, central corneal thickness (CCT), CDR, and VF indices. Although this formula summarizes standard clinical observations, the accuracy of predicting glaucoma conversion, i.e., development of definitive glaucomatous damage in a suspect, was only fair, with the area under the receiver-operating curve (AUC) of 0.68, according to an independent study.…”

Effect of dorzolamide/timolol combination on the visual field in glaucoma

“…An increased intraocular pressure (IOP) is the most important risk factor for developing glaucomatous optic neuropathy that causes visual field defects 1–7. The Early Manifest Glaucoma Trial showed that each increase (or decrease) of 1 mmHg in the IOP was associated with approximately a 10% increase (or decrease) in the risk for progression of visual field loss 8.…”

Effect of 3 years of treatment with a dorzolamide/timolol (1%/0.5%) combination on intraocular pressure

“…Elevation of the intraocular pressure (IOP) is associated with optic nerve damage that leads to visual field defects 1–7. Thus, the primary goal of glaucoma treatment is to reduce the IOP, which can usually be achieved with ocular hypotensive agents.…”