The effect of changes in intraocular pressure on the risk of primary open-angle glaucoma in patients with ocular hypertension: an application of latent class analysis

Feng Gao,Mae O Gordon,Michael A Kass,Stefano Miglior,Julia A Beiser,Valter Torri,J Philip Miller

doi:10.1186/1471-2288-12-151

Abstract

BackgroundPrimary open-angle glaucoma (POAG) is one of the leading causes of blindness in the United States and worldwide. While lowering intraocular pressure (IOP) has been proven to be effective in delaying or preventing the onset of POAG in many large-scale prospective studies, one of the recent hot topics in glaucoma research is the effect of IOP fluctuation (IOP lability) on the risk of developing POAG in treated and untreated subjects.MethodIn this paper, we analyzed data from the Ocular Hypertension Treatment Study (OHTS) and the European Glaucoma Prevention Study (EGPS) for subjects who had at least 2 IOP measurements after randomization prior to POAG diagnosis. We assessed the interrelationships among the baseline covariates, the changes of post-randomization IOP over time, and the risk of developing POAG, using a latent class analysis (LCA) which allows us to identify distinct patterns (latent classes) of IOP trajectories.ResultThe IOP change in OHTS was best described by 6 latent classes differentiated primarily by the mean IOP levels during follow-up. Subjects with high post-randomization mean IOP level and/or large variability were more likely to develop POAG. Five baseline factors were found to be significantly predictive of the IOP classification in OHTS: treatment assignment, baseline IOP, gender, race, and history of hypertension. In separate analyses of EGPS, LCA identified different patterns of IOP change from those in OHTS, but confirmed that subjects with high mean level and large variability were at high risk to develop POAG.ConclusionLCA provides a useful tool to assess the impact of post-randomization IOP level and fluctuation on the risk of developing POAG in patients with ocular hypertension. The incorporation of post-randomization IOP can improve the overall predictive ability of the original model that included only baseline risk factors.

Highlights

Primary open-angle glaucoma (POAG) is one of the leading causes of blindness in the United States and worldwide
latent class analysis (LCA) provides a useful tool to assess the impact of post-randomization intraocular pressure (IOP) level and fluctuation on the risk of developing POAG in patients with ocular hypertension
The hazard ratio (HR) and its 95% confidence interval (CI) of developing POAG in each class were calculated using 1000 bootstrapping samples to account for the uncertainty in class membership

Summary

Introduction

Primary open-angle glaucoma (POAG) is one of the leading causes of blindness in the United States and worldwide. Ocular hypertension is a leading risk factor for the development of primary open-angle glaucoma (POAG) which remains one of the major causes of blindness in the United States and worldwide [1,2,3,4,5]. A recently emerged technique for longitudinal data analysis, latent class analysis (LCA) [14], provides an appealing approach to this question. Rather than dealing with individual measures of fluctuation, LCA identifies distinct patterns of longitudinal profiles based on the combination of summary statistics (i.e., mean level and variability) and provides information complementary to the conventional methods. The class membership is unobserved (latent) and determined by the class-specific parameters in a data-driven basis

Methods

Results

Discussion

Conclusion