Targeted Defect-Mapping Microperimetry in Geographic Atrophy: A Sensitive Functional Outcome Measure for Intervention Trials.

Purpose: To evaluate the effectiveness of targeted defect-mapping microperimetry (DMP) for capturing progressive visual function loss in eyes with a small extent of geographic atrophy (GA). Design: Prospective longitudinal study. Participants: Twenty-seven eyes from 25 participants with <0.75 disc areas of GA, seen over 145 visits in total. Methods: All participants underwent high-density targeted DMP testing of a 4° radius region-of-interest. Two tests were performed at each visit, and participants were reviewed at 3-monthly intervals up to a 24-month period. Spearman rank correlations were calculated to assess structure-function relationships between the proportion of locations missed (PLM; nonresponse to 10-decibel stimuli) on each test and GA extent in the corresponding region tested. Targeted DMP outcome measures were derived based on evaluating the PLM from all test locations, or only from points adjacent to locations that were repeatably nonresponding on both baseline tests. These DMP outcome measures, and GA extent in the central 8° radius region, were compared based on the coefficient of variation (CoV; representing performance for capturing longitudinal changes) and sample size requirements for trials powered to detect a ≥30% treatment effect. Main Outcome Measures: Correlation coefficients, CoV, and sample size estimates. Results: There was a strong and moderate structure-function correlation between the PLM on targeted DMP and GA extent in the corresponding region tested at the cross section and longitudinally, respectively (correlation coefficient = 0.88 and 0.57, respectively). Evaluating PLM from points ≤0.5° adjacent to repeatably nonresponding locations at baseline was the best-performing DMP outcome measure (CoV = 71%), which was comparable with evaluating GA extent in the central 8° region (CoV = 80%). Evaluating this DMP outcome measure reduced the sample size of a 24-month trial by 46% compared with evaluating GA extent. Conclusions: Targeted DMP testing can provide a sensitive functional outcome measure for trials that can capture longitudinal changes as effectively as measuring structural changes in eyes with a small extent of GA. The high structure-function correlations observed suggests that beneficial treatment effects on GA growth would likely be accompanied by corresponding evidence of functional benefit captured by targeted DMP testing. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.