Evaluation of a Primary Open-Angle Glaucoma Prediction Model Using Long-term Intraocular Pressure Variability Data: A Secondary Analysis of 2 Randomized Clinical Trials.

Importance: The contribution of long-term intraocular pressure (IOP) variability to the development of primary open-angle glaucoma is still controversial. Objective: To assess whether long-term IOP variability data improve a prediction model for the development of primary open-angle glaucoma (POAG) in individuals with untreated ocular hypertension. Design, Setting, and Participants: This post hoc secondary analysis of 2 randomized clinical trials included data from 709 of 819 participants in the observation group of the Ocular Hypertension Treatment Study (OHTS) followed up from February 28, 1994, to June 1, 2002, and 397 of 500 participants in the placebo group of the European Glaucoma Prevention Study (EGPS) followed up from January 1, 1997, to September 30, 2003. Data analyses were completed between January 1, 2019, and March 15, 2020. Exposures: The original prediction model for the development of POAG included the following baseline factors: age, IOP, central corneal thickness, vertical cup-disc ratio, and pattern SD. This analysis tested whether substitution of baseline IOP with mean follow-up IOP, SD of IOP, maximum IOP, range of IOP, or coefficient of variation IOP would improve predictive accuracy. Main Outcomes and Measures: The C statistic was used to compare the predictive accuracy of multivariable landmark Cox proportional hazards regression models for the development of POAG. Results: Data from the OHTS consisted of 97 POAG end points from 709 of 819 participants (416 [58.7%] women; 177 [25.0%] African American and 490 [69.1%] white; mean [SD] age, 55.7 [9.59] years; median [range] follow-up, 6.9 [0.96-8.15] years). Data from the EGPS consisted of 44 POAG end points from 397 of 500 participants in the placebo group (201 [50.1%] women; 397 [100%] white; mean [SD] age, 57.8 [9.76] years; median [range] follow-up, 4.9 [1.45-5.76] years). The C statistic for the original prediction model was 0.741. When a measure of follow-up IOP was substituted for baseline IOP in this prediction model, the C statistics were as follows: mean follow-up IOP, 0.784; maximum IOP, 0.781; SD of IOP, 0.745; range of IOP, 0.741; and coefficient of variation IOP, 0.729. The C statistics in the EGPS were similarly ordered. No measure of IOP variability, when added to the prediction model that included mean follow-up IOP, age, central corneal thickness, vertical cup-disc ratio, and pattern SD, increased the C statistic by more than 0.007 in either cohort. Conclusions and Relevance: Evidence from the OHTS and the EGPS suggests that long-term variability does not add substantial explanatory power to the prediction model as to which individuals with untreated ocular hypertension will develop POAG.

Thirteen-Year Follow-up of Optic Disc Hemorrhages in the Ocular Hypertension Treatment Study.

PURPOSE: 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. DESIGN: Prospective cohort study. METHODS: ODHs were evaluated in 3236 eyes of 1618 Ocular Hypertension Treatment Study (OHTS) participants annually using stereoscopic optic disc photographs. The incidence of ODH before and after the development of POAG, the risk of ODH for POAG, and risk factors for ODH were determined using a multivariate proportional hazards regression model. RESULTS: After a median follow-up of 13 years, 1 or more ODHs were detected in 179 eyes of 169 participants. The incidence of ODH was 0.5% per year during an average of 13 years before the development of POAG and 1.2% per year during an average of 6 years after the development of POAG. The cumulative incidence of POAG in eyes with ODH was 25.6% compared with 12.9% in eyes without ODH. The occurrence of an ODH increased the risk of developing POAG 2.6-fold in the multivariate analysis (95% confidence interval, 1.7-4.0; P < .0001). Randomization to the observation group, older age, thinner central corneal thickness, larger vertical cup-to-disc ratio, higher intraocular pressure, and self-reported black race were identified as risk factors for ODH. CONCLUSION: ODH is an independent predictive factor for the development of POAG in patients with ocular hypertension (OHT) and the predictive factors for ODH are very similar to those for POAG in OHT patients.