Customized Evaluation of Progressive Visual Sensitivity Loss in Geographic Atrophy to Improve the Power of Clinical Trials.

PURPOSE

To evaluate the effectiveness of different approaches for customizing the selection of a subset of test locations on defect-mapping microperimetry (DMP) for improving the detection of progressive visual function decline in geographic atrophy (GA).

DESIGN

Prospective longitudinal study.

PARTICIPANTS

Sixty eyes from 53 participants with GA secondary to age-related macular degeneration.

METHODS

Participants underwent 3-monthly DMP testing twice at each visit for up to 24 months, where the extent of deep visual sensitivity losses on each test was determined through single presentations of 10-decibel stimuli at 208 locations within the central 8° radius region. Seven outcome measures were derived, which included evaluating the proportion of locations missed (PLM; showing nonresponse to stimuli) on DMP in a subset of test locations based on their proximity to the GA margin, or to locations neighboring repeatably nonresponding points on 2 baseline tests (i.e., missed both tests at baseline). These outcome measures were compared by their coefficient of variation (CoV; reflecting performance for capturing longitudinal changes) and sample size estimates in a 2-arm trial seeking to detect a ≥30% treatment effect. Changes in GA extent and best-corrected visual acuity (BCVA) were evaluated for comparison.

MAIN OUTCOME MEASURES

Coefficient of variation and sample size estimates.

RESULTS

Evaluating PLM at points immediately adjacent (<1°) to repeatably nonresponding test locations at baseline (CoV = 47%) was the best performing outcome measure on DMP testing. This measure outperformed BCVA (CoV = 188%; < 0.001) at detecting longitudinal changes and was comparable to evaluating GA extent (CoV = 58%;  = 0.097). Sample size requirements in a 24-month trial using this outcome measure on DMP testing were lower by 46% and 94% compared with evaluating GA extent and BCVA, respectively.

CONCLUSIONS

Customized evaluation of DMP functional testing results in regions adjacent to repeatably nonresponding locations at baseline improved the detection of longitudinal changes compared with the evaluation of all test locations. These findings show that it is possible to sensitively capture progressive visual function decline with this approach, supporting its use in future GA treatment trials.

FINANCIAL DISCLOSURES

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.