Translating research into practice: controlled clinical trials and their influence on glaucoma management.

Historically, management strategies for glaucoma have stressed reduction of IOP as the primary goal. Yet, if we question this principle, we find a deficiency of information to support it as the optimal strategy for managing glaucoma patients and those at risk of developing glaucoma. Thus, the practice of lowering IOP in glaucoma management was placed on trial by the 1987 Eddy and Billings report (D. M. Eddy and J. Billings, 1987). Although generally denounced by clinicians, this report nonetheless alerted the ophthalmologic community that success of glaucoma treatment must be measured by endpoints unrelated to IOP and that a controlled trial to demonstrate glaucoma treatment efficacy was necessary. A clinical trial is an experiment. As such, it is the best study design for inferring causality between an exposure (e.g., IOP) and an outcome (e.g., glaucoma), and it is the best methodology for demonstrating treatment efficacy. However, it is important to understand that efficacy is not the same as effectiveness. Whereas "efficacy" is the extent to which a specific intervention produces a beneficial result under ideal conditions, "effectiveness" is the extent to which a specific intervention, when deployed in the field, does what it is intended to do. The influence of study results on the practice of medicine is more a function of demonstrated effectiveness than efficacy of an intervention. All of the completed glaucoma clinica trials reviewed were well performed, and many have had a substantial influence on the philosophy and practice of glaucoma management. The glaucoma clinical trials currently being performed represent the highest standards of clinical trial methodology. This is an exciting time for clinical research on glaucoma. Well accepted dogmas are being challenged, and the ophthalmic community is aggressively addressing difficult issues. Questions being asked are of fundamental importance and addressing them is essential. Particularly exciting in these trials is the fact that IOP is not being considered as an endpoint and that consideration is being given to the previously ignored but extremely important issue of overall patient well-being. Only with time will the ultimate impact of these trials on the philosophy and practice of glaucoma management become evident.