Heterogeneous Visual Function Deficits in Intermediate Age-Related Macular Degeneration: A MACUSTAR Report

Abstract

Objective: To examine the extent to which visual function in Beckman age-related macular degeneration (AMD) disease stages differs from age-similar peers with no AMD and, using reference limits derived from those with no AMD, test the hypothesis that people with intermediate AMD (iAMD) have heterogeneous visual function deficits.

Design: Cross-sectional analyses of a range of baseline visual function measures from the MACUSTAR study-an international, multicenter (n = 20), noninterventional clinical trial.

Participants: Five hundred eighty-five participants with iAMD (67% female, mean [standard deviation] age 72 [7] years) were recruited alongside 56 with no AMD (59% female, 68 [6]), 34 with early AMD (79% female, 72 [6]), and 43 with late AMD (49% female, 75 [6]).

Methods: Participants performed best-corrected visual acuity (BCVA), low luminance visual acuity (LLVA), Moorfields acuity test (MAT), Pelli-Robson contrast sensitivity (PR-CS), small print standardized International reading speed test (SPS), mesopic and scotopic average threshold (MesAT and ScoAT; macular integrity assessment, iCare), and rod intercept time (RIT; AdaptDx, Lumithera).

Main outcome measures: Relationship between each visual function measure and disease classification was examined by linear regression adjusted for age, sex, and phakic status. No AMD data were used to estimate normal reference limits for each visual function test. Intermediate AMD scores were dichotomized against reference limits, and the proportion worse than each limit was calculated.

Results: Relative to no AMD, SPS was significantly worse in early AMD (P = 0.001); all measures except SPS were significantly reduced in iAMD (P < 0.02), and all measures were markedly reduced in late AMD (P < 0.0001). Thirty-one point three percent of iAMD participants breached reference limits for PR-CS, 29.4% for RIT, 24.1% for LLVA, 23.2% for MAT, 20.5% for BCVA, 19.8% for MesAT, 17.9% for ScoAT, and 12.6% for SPS. Of the iAMD participants, 69.6% and 42.7% breached ≥1 and ≥2 reference limits, respectively, whereas 33.6% and 5.7% would be expected by chance.

Conclusions: A large proportion of people with structurally defined iAMD exhibit heterogeneous visual function deficits outside normal reference limits. This observation may be relevant for the design and inclusion criteria of future interventional trials.

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; Visual dysfunction; Visual function.

Figure 1

Distribution of the visual function measures by disease classification. Red dashed line indicates reference limit for each test based on no AMD data. AMD = age-related macular degeneration; BCVA = best-corrected visual acuity; dB = decibel; iAMD = intermediate age-related macular degeneration; LLVA = low luminance visual acuity; LogCS = logarithm of contrast sensitivity; logMAR = logarithm of the minimum angle of resolution; MAT = Moorfields acuity test; MesAT = mesopic average threshold; PR-CS = Pelli-Robson contrast sensitivity; RIT = rod intercept time; ScoAT = scotopic average threshold; SPS = small print standardized International reading speed test; wpm = words per minute.

Figure 2

UpSet plot describing the number and extent of reference limits breached in participants with iAMD. Horizontal black bars indicate the set size or number of iAMD participants who breached the reference limit for each visual function (VF) test shown by the adjacent label. Vertical black bars indicate the intersection size or number of iAMD participants who breached the reference limit of the VF test(s) indicated by the filled black circles beneath. For example, the leftmost vertical black bar indicates that 59 iAMD participants breached the RIT reference limit only, while the rightmost vertical black bar indicates that 4 iAMD participants breached the reference limit on all 8 visual function tests. BCVA = best-corrected visual acuity; iAMD = intermediate age-related macular degeneration; LLVA = low luminance visual acuity; MAT = Moorfields acuity test; MesAT = mesopic average threshold; PR-CS = Pelli-Robson contrast sensitivity; RIT = rod intercept time; ScoAT = scotopic average threshold; SPS = small print standardized International reading speed test.