In 1995, WC Stewart stated that, ”In the future, modifiable risk factors for chronic open-angle glaucoma may become known.”97
Yet, studies to date have not identified an established modifiable risk factor for POAG other than IOP. There may be several explanations for this. First, some exposures are complex (e.g. diet) and do not represent a single biologic agent. These complex exposures may exhibit what we would coin ‘environmental antagonistic pleiotropism’, that is they simultaneously generate biologic responses that offset one another. In one hypothetical example, “perceived stress” may increase epinephrine and lower IOP while also increasing endogenous steroid levels which could raise IOP. Second, environmental exposures may be modified by genetic factors. For example, while moderate-to-high alcohol consumption may only marginally alter the risk of POAG, slow metabolizers of alcohol may enjoy a protective effect from lower alcohol consumption. There are common polymorphisms in the genes that metabolize alcohol and slow its metabolism; interaction between these polymorphisms, alcohol consumption and POAG should be explored.98
Third, POAG exhibits considerable phenotypic heterogeneity, thus it would be very informative to conduct analyses where cases with specific patterns of visual field loss, cases with different levels of IOP associated with initial signs of disease or cases with family history are examined separately. Finally, the absence of environmental risk factors for POAG may be related to methodological issues such as small sample size of studies, short follow-up periods and the paucity of studies, especially those with prospective study designs. Furthermore, biomarker studies may yield more significant associations with POAG since the biologic response to an exposure may be more important than the exposure itself in triggering disease.
Only randomized clinical trials can demonstrate whether lifestyle factors, behaviors or diet will modify the risk of POAG. However, randomized trials cannot be conducted on all exposures (e.g. cigarette smoking or alcohol) and thus the results from epidemiologic studies would provide the best evidence to date.
In this review, we have examined the evidence on whether environmental factors are related to developing glaucoma. How do we answer the questions from newly diagnosed glaucoma patients on lifestyle behaviors and their relation to POAG? There is even scarcer data on lifestyle factors and their influence on disease progression. However, rather than default to the view that patients should simply comply with medical therapy and follow-up recommendations (which of course is true), we also suggest advocating for activities consistent with overall good health such as avoidance of smoking, moderate exercise and a diet high in fruits and vegetables. The weight of the current medical is not sufficiently strong to make broad recommendations regarding activities that glaucoma patients should avoid because they elevate IOP such as certain yoga positions, playing high wind instruments for long periods of time, and drinking large amounts of caffeinated coffee.
We suspect that advances in the fields of glaucoma genetics and neuroprotection will assist the discovery of environmental risk factors for POAG. Specifically, we hypothesize that the identification and characterization of POAG susceptibility genes or factors that favorably alter the rate of retinal ganglion cell apoptosis will reveal important biochemical pathways operative during the pre-clinical phase of the disease as well as novel environmental factors that modify these pathways. Ultimately such work could lead to the discovery of environmental factors that contribute to disease in certain genetic settings. The identification of these gene-environment interaction terms related to POAG could lead to genotype-specific lifetstyle modification strategies that reduce the burden of glaucomatous visual loss.