A Comparison of Visual Field Progression Criteria of 3 Major Glaucoma Trials in Early Manifest Glaucoma Trial Patients Anders Heijl, MD, PhD, 1 Boel Bengtsson, PhD, 1 Balwantray C. Chauhan, PhD, 2 Marc F. Lieberman, MD, 3 Ian Cunliffe, MD, FRCS, 4 Leslie Hyman, PhD, 5 M. Cristina Leske, MD, MPH 5 Purpose: Three major glaucoma trials, all using the same Humphrey visual field tests, specified different criteria to define visual field progression. This article compares the performance of these criteria with a reference standard of unanimous classifications by 3 independent glaucoma experts. Design: Longitudinal, comparative study of diagnostic criteria. Participants and Controls: Two hundred forty-five patients with manifest glaucoma in the Early Manifest Glaucoma Trial (EMGT). Methods: Visual field series of 1 eye of each of 245 EMGT patients were classified by 3 independent glaucoma specialists as definitely progressing, definitely nonprogressing, or neither. Field series that were classified in the first 2 categories by all 3 experts met the reference standards for the progressing and nonprogressing groups and were analyzed according to the progression criteria of the Advanced Glaucoma Intervention Study (AGIS), the Collaborative Initial Glaucoma Treatment Study (CIGTS), and the EMGT. Sensi- tivity, specificity, time to progression, and sustainability were calculated. Main Outcome Measures: Progression, nonprogression, sensitivity, specificity, time to progression, and sustainability. Results: Seventy-seven field series were definitely progressing, and 95 series were definitely nonprogress- ing. Among progressing eyes, 45 (58%) of 77 were identified using AGIS criteria, 58 (75%) of 77 were identified with CIGTS criteria, and 74 (96%) of 77 were identified with EMGT criteria; all comparisons of sensitivities were significant, simultaneous (P0.001), and pairwise (P0.01). The specificity for EMGT criteria was 89%, lower (P0.05) than that of AGIS (98%) and CIGTS (99%) criteria. Median time to progression was considerably shorter with EMGT criteria (33 months; 95% confidence interval [CI], 30 –36 months) than with AGIS (66 months; 95% CI, 57–78 months) and CIGTS (55 months; 95% CI, 48 – 66 months) criteria. Sustainability increased with time after progression; it averaged 79%, 84%, and 81%, respectively, for AGIS, CIGTS, and EMGT criteria during the first year after the first progression and 95%, 100%, and 93% during the fourth year after progression. Conclusions: The EMGT criteria identified progression earlier and more often than AGIS and CIGTS criteria. Specificity was good for all criteria but was better with AGIS and CIGTS than with EMGT criteria. Sustainability was high for all 3 sets of criteria and best for CIGTS criteria and increased with time after progression. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2008;115:1557–1565 © 2008 by the American Academy of Ophthalmology. The Early Manifest Glaucoma Trial (EMGT), 1,2 the Ad- vanced Glaucoma Intervention Study (AGIS), 3 and the Col- laborative Initial Glaucoma Treatment Study (CIGTS) 4 are 3 large, randomized clinical trials that studied the effects of treatment on disease progression in open-angle glaucoma. Worsening of visual field status is an important sign of such progression, and rigorous visual field testing using standard computerized static perimetry thus has been included in the protocols of all 3 studies. Furthermore, all 3 trials have used the same test instrument, the Humphrey perimeter (Carl Zeiss Meditec, Dublin, CA) and the same Full-Threshold algorithm for follow-up. However, the 3 studies used dif- ferent predefined criteria to identify field progression. The ability to identify visual field progression (i.e., to distin- guish between visual field worsening and nonprogression) depends on the criteria used to interpret the perimetric results. Ideally, interpretation criteria should identify dis- ease progression as early as possible, while avoiding false- positive results. Effective visual field interpretation criteria are highly desirable, but currently there is no broad agreement on the best way to analyze visual field series from glaucomatous eyes. Assessments of the performance of different sets of criteria are valuable; such results may help both to select the most appropriate rules for clinical usage today and to pro- vide a basis for future development in this area. A large number of studies have compared the perfor- mance of different sets of criteria to assess progression in series of field tests from glaucomatous eyes. 5–9 One article compared AGIS, CIGTS, and EMGT criteria, 10 showing that the field interpretation outcomes indeed differ depend- ing on the criterion applied. The aim of the current study 1557 © 2008 by the American Academy of Ophthalmology ISSN 0161-6420/08/$–see front matter Published by Elsevier Inc. doi:10.1016/j.ophtha.2008.02.005