Reading Performance in Geographic Atrophy: Comparison of Different Reading Speed Measures for Capturing Longitudinal Changes

Abstract

Purpose: To compare different reading speed measures for capturing longitudinal visual function changes in eyes with geographic atrophy (GA) secondary to age-related macular degeneration.

Design: Analysis of data from Chroma (NCT02247479) and Spectri (NCT02247531), 2 identically designed, phase III, double-masked, randomized controlled clinical trials for lampalizumab.

Participants: Nine hundred forty participants aged ≥50 years old with bilateral GA, who completed monocular testing of reading speed at ≥3 visits over >1-year follow-up.

Methods: Monocular reading speed was assessed using the Minnesota Low-Vision Reading Test (MNRead). Four different reading speed measures were derived and compared: reading speed of the fastest sentence read (RS₁), mean reading speed of the 3 fastest sentences read (RS₂), mean reading speed of the sentences larger than the critical print size (RS₃), and mean reading speed of the 10 largest print sizes (termed the Reading Accessibility Index [ACC]).

Main outcome measures: Coefficient of variation (CV), with lower values reflecting better performance of a measure for capturing longitudinal change relative to interindividual variability.

Results: All 4 reading speed measures showed a significant decline at 48, 72, and 96 weeks from baseline (P < 0.001 for all). The CVs for ACC and RS₂ (204% and 208%, respectively) were lower than for RS₁ (255%; P ≤ 0.002) and RS₃ (224%; P ≥ 0.068) for detecting change from baseline at 48 weeks, but these 2 measures were not significantly different from each other (P = 0.362). There were also statistically significant, but weak, negative correlations between the change from baseline at 48 weeks for all 4 reading speed measures with GA area on fundus autofluorescence imaging (ρ = -0.13 to -0.15; all P < 0.001).

Conclusions: The mean reading speed derived from either the 10 print sizes found in everyday life (ACC) or the fastest 3 sentences read (RS₂) was better than 2 widely used measures (RS₁ and RS₃) at capturing progressive functional decline in eyes with GA and may be the preferred measures in future clinical trials and studies. All reading speed measures also showed an expected progressive decline over time, but they only showed a weak correlation with GA growth.

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

Keywords: Age-related macular degeneration; Geographic atrophy; Reading speed; Visual acuity; Visual function.

Figure 1

Example illustrating how the 4 reading speed measures are calculated in this study based on a plot of the reading speed (in words per minute) across different print sizes (in logarithm minimum of the angle of resolution [logMAR]). RS₁ = reading speed of the fastest sentence read (indicated by “∗∗”); RS₂ = mean reading speed of the 3 fastest sentences read (indicated by “∗” and “∗∗”); RS₃ = mean reading speed of the sentences larger than the critical print size (CPS) as shown by the solid black horizontal line. The CPS (indicated by the vertical dotted line) in this study was defined as the larger of the print size, where the smaller print sizes were read at a logarithm-transformed speed that was 1.96 times the standard deviation below the average of the previous larger print sizes, or 5% slower than the average of the previous larger print sizes (both inclusive of the critical print size; the solid dashed horizontal line represents the lower limit of the reading speed used for determining the CPS, which corresponded to reading speed that was 1.96 times the standard deviation below the average of the previous larger print sizes for the logarithm-transformed reading speed in this example). ACC = Reading Accessibility Index, defined as the mean reading speed of the 10 largest print sizes (outlined in the gray rectangle).

Figure 2

Plots of the change from baseline over time for (A) reading speed (RS) measures for 3 different definitions (Definition 1 [RS₁] = speed of the fastest sentence read; Definition 2 [RS₂] = mean reading speed of the fastest 3 sentences read; Definition 3 [RS₃] = mean reading speed of the sentences larger than the critical print size; all measured in words per minute [WPM]), (B) the Reading Accessibility Index (ACC; mean reading speed across the 10 largest print size, divided by 200), (C) best-corrected visual acuity (BCVA) and low luminance visual acuity (LLVA), (D) reading acuity (RA), and (E and F) geographic atrophy (GA) area (square root transformed and untransformed, respectively). Error bars represent the 95% confidence interval of the mean.

Figure 3

Strength of correlation (based on the Spearman rank correlation coefficient [ρ]; with higher absolute values indicated by darker shading) between the change from baseline at 48 weeks for the different reading speed (RS) measures (Definition 1 [RS₁] = speed of the fastest sentence read; Definition 2 [RS₂] = mean reading speed of the fastest 3 sentences read; Definition 3 [RS₃] = mean reading speed of the sentences larger than the critical print size; Reading Accessibility Index [ACC] = mean reading speed across the 10 largest print size, divided by 200), acuity measures (best-corrected visual acuity [BCVA]; low luminance visual acuity [LLVA]; reading acuity [RA]) and geographic atrophy (GA) area measures (square root-transformed GA area [GA1]; untransformed GA area [GA2]).