Author: Sandrine H. Künzel (Germany)
Co-authors: Moritz Lindner, Matthias Schmid, Steffen Schmitz-Valckenberg, Frank G. Holz, Monika Fleckenstein, Maximilian Pfau
Purpose
Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in western countries. High prevalence, expected increase in patients, and lack of treatment options make especially its dry late-stage, i.e. geographic atrophy (GA), an important study subject. Hereby, enlargement of GA, detected by fundus autofluorescence (FAF) imaging, is accepted as endpoint for clinical trials. However, the impact of GA topography and enlargement on the reading performance is yet understudied. In this analysis, we investigated the complex relationship between the topography of GA lesions, the visual function, and the reading performance and we determined the longitudinal change of the reading performance.
Setting/Venue
150 eyes of 85 patients with a median age [IQR] of 78.9[9.6] years with GA participating in the longitudinal, non-interventional, prospective natural history study ‘Directional Spread in Geographic Atrophy’ (NCT02051998) at the Department of Ophthalmology, University of Bonn, Germany, were included in the analysis.
Methods
Clinical assessment included age, gender, best-corrected visual acuity (BCVA), low luminance visual acuity (LLVA), central visual field loss (foveal sparing), reading acuity, and speed. The BCVA, LLVA were assessed using the Early Treatment Diabetic Retinopathy Study. Reading acuity and reading speed were assessed using the RADNER-Charts. All patients underwent 30°x30° FAF imaging and infrared reflectance imaging (Heidelberg Engineering, Germany). The images were semi-automatically 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. Nested-resampling was applied to obtain estimates of the prediction accuracy. Hereby, the mean coefficient-of-determination (R2) served as measure of prediction accuracy.
Results
Reading performance was impaired with a monocular reading acuity of 0.90[0.9] logMAR and a reading speed of 52.82[123.0] words-per-minute. In the multivariable cross-sectional analysis, (i) best-corrected visual acuity, (ii) area of geographic atrophy in the central ETDRS-subfield, (iii) classification of non-center vs. center-involving geographic atrophy, and (iv) area of geographic atrophy in the inner-right ETDRS-subfield showed strongest associations with reading acuity (cross-validated R2(Reading Acuity)=0.69). Regarding reading speed, the most relevant variables were (i) best-corrected visual acuity, (ii) low luminance visual acuity, (iii) area of geographic atrophy in the central, (iv) in the inner-right, and (v) in the inner-upper ETDRS-subfield (cross-validated R2(Reading Speed)=0.67). In the longitudinal analysis, a similar prediction accuracy for reading performance was determined. Prediction accuracy did not improve when follow-up time was added as an independent variable. Binocular reading performance did not differ significantly from reading performance in the better eye.
Conlusions
Reading acuity and speed are significantly impaired in geographic atrophy patients. Its association with visual functional and structural biomarkers supports the validity of reading performance as a meaningful endpoint in clinical trials. To benefit patients in clinical and low vision care, measures should be focused primarily on the better eye.
Financial Disclosure
Funding/Support: This work was supported by the German Ophthalmological Society (DOG dissertation grant to SHK), the German Research Foundation [DFG grant PF 950/1-1 to MP; DFG grant 658/4-1 and 658/4-2 to MF; University Hospital Gießen and Marburg Research Funds (15/2020MR to ML)] and the BONFOR GEROK Program of the Faculty of Medicine, University of Bonn [Grant No O-137.0022 and O-137.0025 to MP]. Financial Disclosures: CenterVue SpA, Padova, Italy has provided research material (S-MAIA) for the conduct of this study. CenterVue had no role in the design or conduct of the experiments.
Comments
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