A LTHOUGH LOWERING OF INTRAOCULAR PRESSURE is a principal guide for therapy of chronic glaucoma and for determining the efficacy of treatment in scientific studies, it is really the preservation of axons (structure) or visual capabilities (function) that matters to the glaucoma patient in the long run. The authors met to try to define progression of the disease using old and new methods used to quantify the structural and functional status of glaucoma. We considered this in the context of clinical care and scientific studies, especially as treatment modalities intended to affect blood flow or neural survival (rather than simply lowering the intraocular pressure) are emerging. We hoped to develop concrete criteria that might be suggested for widespread use to create uniformity in scientific studies and clinical practice. When we considered what methods and criteria of measured parameters might be suitable to judge glaucomatous deterioration, it quickly became apparent that the needs differed according to purpose. For example, evaluation of the course of the disease in an individual patient is different from identifying small differences in the average course between two or more study groups and also different from ascertaining the safety of each individual enrolled in a clinical trial. In some circumstances, the progression of one parameter may be more appropriate than others, particularly because scientific studies may vary in purposes. The demonstration of adequate axonal nutrition, for example, may require progression in a parameter that is different than the protection from the parameter used to assess protection from harm caused by an ischemic insult. Finally, emerging or new technology may provide a means of evaluation of special advantage. Therefore, no single current method, measured parameter, or criterion appeared suitable for all these circumstances. Indeed, most clinical studies devise new criteria to meet their particular needs or use new methods that became available since prior studies were designed,1 which makes comparison between studies difficult. For this reason, we abandoned the effort to define specific parameters to be measured, particular methods of examination currently available or in use, or particular criteria to be applied to available measurements that we might suggest as “the standard” to be used for all clinical and research purposes. Instead, we considered the characteristics that would make a determination of glaucoma progression acceptable. The following guidelines and considerations are proposed: 1. The measurement and criteria used in clinical studies should have good performance in recognizing progression and in separating the groups being compared (stable versus unstable, rapid deterioration versus less rapid, and so forth). This requires good reproducibility of the tests and that the parameter used have small and known biological fluctuation in an individual from one time to another. 2. The measured values and criteria that provide good sensitivity and specificity in recognizing progression of the disease may very well differ from those that are sensitive and specific in recognizing the presence or absence of the disease. 3. The measurement should be accepted as relevant to the course of the disease and its clinical outcome. This may include direct measurements of structure (axon count) or function (vision) exemplified, for example, by retinal nerve fiber measurements, optic disk parameters, electrophysiologic measurements of ganglion cell activity, visual field as well as other visual psychophysical testing. 4. In principle, an acceptable measurement may also be a short-term surrogate of long-term outcome, that is, some predictive parameter for which there has been documented linkage to future progression and outcome. Currently, intraocular pressure is accepted as a surrogate for expected Accepted for publication July 18, 2000. From the Bascom Palmer Eye Institute, University of Miami, Miami, Florida (Dr Anderson); Department of Ophthalmology, University of British Columbia, Vancouver, BC, Canada (Dr Drance); Director of Diagnostic Research Discoveries in Sight Research Labs, Devers Eye Institute, Portland, Oregon (Dr Johnson); Departments of Ophthalmology and Physiology & Biophysics Dalhousie University, Halifax, N.S. Canada (Dr Chauhan); Zeiss Humphrey Systems, Dublin, California (Dr Patella); Division of Disease Control, Department of International Health, Johns Hopkins University, Baltimore, Maryland (Dr Katz). Reprint requests to Stephen M. Drance, OC, MD, 1561 Wesbrook Crescent, Vancouver, BC V6T 1V9, Canada.