Short-term Detection of Fast Progressors in Glaucoma

Purpose: To evaluate the performance of an intensive, clustered testing approach in identifying eyes with rapid glaucoma progression over 6 months in the Fast Progression Assessment through Clustered Evaluation (Fast-PACE) Study. Design: Prospective cohort study. Participants: A total of 125 eyes from 65 primary open-angle glaucoma (POAG) subjects. Methods: Subjects underwent 2 sets of 5 weekly visits (clusters) separated by an average of 6 months and then were followed with single visits every 6 months for an overall mean follow-up of 25 months (mean of 17 tests). Each visit consisted of testing with standard automated perimetry (SAP) 24-2 and 10-2, and spectral domain OCT (SD-OCT). Progression was assessed using trend analyses of SAP mean deviation (MD) and retinal nerve fiber layer (RNFL) thickness. Generalized estimating equations were applied to adjust for correlations between eyes for confidence interval (CI) estimation and hypothesis testing. Main Outcome Measures: Diagnostic accuracy of the 6-month clustering period to identify progression detected during the overall follow-up. Results: A total of 19 of 125 eyes (15%, CI, 9%-24%)- 24%) progressed based on SAP 24-2 MD over the 6-month clustering period. A total of 14 eyes (11%, CI, 6%-20%)- 20%) progressed on SAP 10-2 MD, and 16 eyes (13%, CI, 8%-21%)- 21%) progressed by RNFL thickness, with 30 of 125 eyes (24%, CI, 16%-34%)- 34%) progressing by function, structure, or both. Of the 35 eyes progressing during the overall follow-up, 25 had progressed during the 6-month clustering period, for a sensitivity of 71% (CI, 53%-85%).- 85%). Of the 90 eyes that did not progress during the overall follow-up, 85 also did not progress during the 6-month period, for a specificity of 94% (CI, 88%-98%).- 98%). Of the 14 eyes considered fast progressors by SAP 24-2, SAP 10-2, or SD-OCT during the overall follow-up, 13 were identified as progressing during the 6-month cluster period, for a sensitivity of 93% (CI, 66%-100%)- 100%) for identifying fast progression with a specificity of 85% (CI, 77%-90%).- 90%). Conclusions: Clustered testing in the Fast-PACE Study detected fast-progressing glaucoma eyes over months. The methodology could be applied in clinical trials investigating interventions to slow glaucoma progression and may be of value for short-term assessment of high-risk subjects.