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Original Investigation
September 30, 2021

Association of Reading Performance in Geographic Atrophy Secondary to Age-Related Macular Degeneration With Visual Function and Structural Biomarkers

Author Affiliations
  • 1Department of Ophthalmology, University of Bonn, Bonn, Germany
  • 2Nuffield Laboratory of Ophthalmology, Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
  • 3Institute for Physiology and Pathophysiology, Department of Neurophysiology, Philipps-University Marburg, Marburg, Germany
  • 4Institute for Numerical Simulation, University of Bonn, Bonn, Germany
  • 5Institute for Medical Biometry, Informatics and Epidemiology, Medical Faculty, University of Bonn, Bonn, Germany
  • 6John A. Moran Eye Center, University of Utah, Salt Lake City
  • 7Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland
JAMA Ophthalmol. Published online September 30, 2021. doi:10.1001/jamaophthalmol.2021.3826
Key Points

Question  What is the association of reading performance in patients with geographic atrophy secondary to age-related macular degeneration with established visual function and structural biomarkers?

Findings  In this cohort study of 150 eyes of 85 participants, reading acuity was most strongly associated with best-corrected visual acuity and geographic atrophy area in the central and inner-right Early Treatment Diabetic Retinopathy Study subfield. Regarding reading speed, the most associated variables were best-corrected visual acuity, low-luminance visual acuity, and geographic atrophy area in the central, the inner-right, and the inner-upper Early Treatment Diabetic Retinopathy Study subfields.

Meaning  The association of reading performance with visual functional and structural biomarkers supports the validity of reading performance as an end point in clinical trials.

Abstract

Importance  As a disabling and frequent disease, geographic atrophy secondary to age-related macular degeneration (AMD) constitutes an important study subject. Emerging clinical trials require suitable end points. The characterization and validation of reading performance as a functional outcome parameter is warranted.

Objective  To prospectively evaluate reading performance in geographic atrophy and to assess its association with established visual function assessments and structural biomarkers.

Design, Setting, and Participants  The noninterventional, prospective natural history Directional Spread in Geographic Atrophy study included patients with geographic atrophy secondary to AMD who were recruited at the University Hospital in Bonn, Germany. Participants were enrolled from June 2013 to June 2016. Analysis began December 2019 and ended January 2021.

Main Outcomes and Measures  Reading acuity and reading speed were assessed using Radner charts. Longitudinal fundus autofluorescence and infrared reflectance images were semiautomatically annotated for geographic atrophy, followed by extraction of shape-descriptive variables. Linear mixed-effects models were applied to investigate the association of those variables with reading performance.

Results  A total of 150 eyes of 85 participants were included in this study (median [IQR] age, 77.9 [72.4-82.1] years; 51 women [60%]; 34 men [40%]). Reading performance was impaired with a median (IQR) monocular reading acuity of 0.9 (0.4-1.3) logarithm of the reading acuity determination and a reading speed of 52.8 (0-123) words per minute. In the multivariable cross-sectional analysis, best-corrected visual acuity, area of geographic atrophy in the central Early Treatment Diabetic Retinopathy Study (ETDRS) subfield, classification of noncenter vs center-involving geographic atrophy, and area of geographic atrophy in the inner-right ETDRS subfield showed strongest associations with reading acuity (cross-validated R2for reading acuity = 0.69). Regarding reading speed, the most relevant variables were best-corrected visual acuity, low-luminance visual acuity, area of geographic atrophy in the central ETDRS subfield, in the inner-right ETDRS subfield, and in the inner-upper ETDRS subfield (R2 for reading speed = 0.67). In the longitudinal analysis, a similar prediction accuracy for reading performance was determined (R2 for reading acuity = 0.73; R2 for reading speed = 0.70). Prediction accuracy did not improve when follow-up time was added as an independent variable. Binocular reading performance did not differ from reading performance in the better-seeing eye.

Conclusions and Relevance  The association of reading acuity and speed with visual functional and structural biomarkers supports the validity of reading performance as a meaningful end point in clinical trials. These findings suggest that measures in clinical and low-vision care for patients with geographic atrophy should focus primarily on the better-seeing eye.

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