Causal inference in primary open angle glaucoma: specific discussion on intraocular pressure.

OBJECTIVES: As the first part of a comprehensive review of the concept of causal inference in epidemiology, this article explains how causal inference is established in epidemiology and applies these methods to evaluate the evidence in favor or against the causal association between intraocular pressure (IOP) and primary open angle glaucoma (POAG) as an example.
METHODS: After an introduction to causal inference in epidemiology and general guidelines for assessment of the causal relationship, the association between IOP and POAG will be evaluated in the context of these guidelines and the categories suggested by the Surgeon General's report.
RESULTS: The literature indicates a consistent strong association between IOP and POAG and there is no strong evidence against temporal precedence. The association is biologically plausible, coherent with scientific principles, and has noticeable biological gradient. However, it seems that IOP is not specific for POAG and vice versa.
CONCLUSION: Despite the absence of specificity, we conclude that the evidence is sufficient to infer a causal relationship between IOP and POAG. In sum, based on the literature and our current knowledge of glaucoma, currently most competing causes are not strong enough to confront the causal role of IOP.