Visual Function Tests as Potential Biomarkers in Age-Related Macular Degeneration

PURPOSE. To evaluate the potential of psychophysical assessments of retinal function to provide diagnostic biomarkers of early age-related macular degeneration (AMD). METHODS. Unilateral visual function was assessed in 221 participants (72.86 +/- 9.94 years; 67% women) with early AMD (visual acuity better than 20/60) and 109 controls (73.07 +/- 10.32 years; 65% women). Psychophysical assessment included steady state thresholds (4- and 14-Hz flicker and red and blue color) and dynamic tests (photostress recovery [PSR] and dark adaptation [DA]). All test parameters were compared in terms of their diagnostic capacity (sensitivity and specificity), reproducibility, and clinical applicability (test duration and participant's perception of test difficulty). AMD status was determined by digital photography, according to the International Classification and Grading System. RESULTS. All functional measurements were significantly worse, on average, in the AMD group than in the control group (P < 0.001). Static and dynamic parameters showed weak correlations (range, 0.003-0.225). Rod recovery in DA and cone recovery in PSR had the best diagnostic capacity (area under curve [AUC], receiver operating characteristic [ROC] analysis, 0.93 +/- 0.016 and 0.85 +/- 0.021, respectively). Considering diagnostic capacity together with test reproducibility and clinical applicability, the 14-Hz flicker gave the best outcome, followed by PSR. Combination of these two tests detected 71% of abnormal early AMD cases. CONCLUSIONS. All the visual function tests had good diagnostic capacity. Combination of the 14-Hz flicker thresholds and dynamics of the PSR test provided optimal quantitative assessment of retinal function in early AMD, suggesting that this set is a potentially useful clinical tool for following progression of early AMD and assessing the efficacy of interventions. (Invest Ophthalmol Vis Sci. 2011; 52: 9457-9469) DOI:10.1167/iovs.10-7043