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Editors Selection IGR 15-4

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Comment by Keith Martin on:

20979 Cerebrospinal fluid pressure is decreased in primary open-angle glaucoma, Berdahl JP; Allingham RR; Johnson DH, Ophthalmology, 2008; 115: 763-768

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Berdahl et al. present a provocative study that gives us reason to wonder whether we have been looking at the wrong side of the optic nerve in primary open-angle glaucoma (POAG) and they should be commended for that. My comments will be limited to using the case-control study design to discover new disease etiologies.Case-control studies have both misled us (coffee and pancreatic cancer¹) and enlightened us (aspirin and Reyes syndrome²), but by themselves do not provide evidence of a direct relation between the exposure of interest and disease. The declarative study title, Cerebrospinal Fluid Pressure is Decreased in Primary Open-Angle Glaucoma, is rather bold although the authors do acknowledge some of the potential pitfalls in their study. There are other potential issues to consider. This is a retrospective analysis of cases that may not be representative of the population at risk for POAG. The percentage of the population that was under ophthalmic surveillance is not reported. Thus we do not know if subjects with an eye exam are different in some way versus those that did not. Controls were neither individually matched (matched on pre-defined criteria) nor frequency matched (if 20% of cases are over 65 years old, then 20% of controls should also be over 65 years old) to cases. The authors appropriately construct a multivariate model to assess whether the relation between cerebrospinal fluid (CSF) pressure and POAG is confounded by other variables but the sample size is too small to make those results meaningful. Furthermore it is unclear if critical variables such as gender, age and case-control status are entered into that model. Regardless of the study limitations, the findings are worthy of confirmation in an appropriately designed prospective sample. The availability of a non-invasive, validated measure of CSF pressure would facilitate such a study.

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