Validated prediction model for the development of primary open-angle glaucoma in individuals with ocular hypertension

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 and 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 \u3c72 for systematic overestimation/underestimation of predicted risk. The 2 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\u2019 median follow-up) and EGPS placebo group (n = 500; 4.8 years\u2019 median follow-up). Testing Data were collected on demographic characteristics, medical history, ocular examination visual fields (VFs), and optic disc photographs. Main Outcome Measure Development of reproducible VF abnormality or optic disc progression as determined by masked readers and attributed to POAG by a masked end point committee. Results The same predictors for the development of POAG were identified independently in both the OHTS observation group and the EGPS placebo group\u2014baseline age, intraocular pressure, central corneal thickness, vertical cup-to-disc ratio, and Humphrey VF pattern standard deviation. The pooled multivariate model for the development of POAG had good discrimination (c statistic, 0.74) and accurate estimation of POAG risk (calibration \u3c72, 7.05). 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\u2013EGPS predictive model, has high precision and will be useful for clinicians and patients in deciding the frequency of tests and examinations during follow-up and advisability of initiating preventive treatment

Evaluation of Progressive Neuroretinal Rim Loss as a Surrogate End Point for Development of Visual Field Loss in Glaucoma

PURPOSE: To evaluate the validity of using progressive neuroretinal rim area loss as a surrogate endpoint for development of visual field loss in glaucoma. DESIGN: Prospective observational cohort study. PARTICIPANTS: The study group included 492 eyes of 328 patients classified as suspected of having glaucoma at the baseline visit. These eyes had an average of 7.4 ± 2.8 confocal scanning laser ophthalmoscopy (CSLO) images during a mean follow-up time of 6.6 ± 1.6 years. METHODS: Rim area measurements were acquired with CSLO during follow-up. The visual field endpoint was considered as development of 3 consecutive abnormal visual fields on standard automated perimetry. Strong predictive ability and large proportion of treatment effect explained (PTE) are requisites for a suitable surrogate endpoint. A joint longitudinal survival model was used to evaluate the ability of rates of rim area loss in predicting visual field development, adjusting for confounding variables (baseline age, race and corneal thickness, and follow-up measurements of intraocular pressure [IOP] and pattern standard deviation). The PTE was calculated comparing the effect of IOP on the risk of development of visual field loss when incorporating rim area loss in the same model versus the effect of IOP in the model excluding rim area measurements. MAIN OUTCOME MEASURES: Predictive strength measured by survival-adapted R(2) and PTE. RESULTS: Sixty-two of 492 (13%) eyes developed visual field loss during follow-up. The mean rate of rim area change in eyes that developed visual field loss was −0.011mm(2)/year versus −0.003mm(2)/year in those that did not (P <0.001). In the multivariable model, each 0.01mm(2)/year faster rate of rim area loss was associated with a 2.94 higher risk of visual field loss (hazard ratio = 2.94; 95% confidence interval: 1.38 – 6.23; P = 0.005). R(2) values were 62% and 81% for univariable and multivariable models, respectively. The PTE was 65%. CONCLUSION: Progressive rim area loss was highly predictive of development of visual field loss in glaucoma and explained a significant proportion of treatment effect on the clinically relevant outcome. These findings suggest that rim area measurements may be suitable surrogate endpoints in glaucoma clinical trials