Retest variability and patient reliability indices of quantitative fundus autofluorescence in age-related macular degeneration: a MACUSTAR study report

Abstract

This study aimed to determine the retest variability of quantitative fundus autofluorescence (QAF) in patients with and without age-related macular degeneration (AMD) and evaluate the predictive value of patient reliability indices on retest reliability. A total of 132 eyes from 68 patients were examined, including healthy individuals and those with various stages of AMD. Duplicate QAF imaging was conducted at baseline and 2 weeks later across six study sites. Intraclass correlation (ICC) analysis was used to evaluate the consistency of imaging, and mean opinion scores (MOS) of image quality were generated by two researchers. The contribution of MOS and other factors to retest variation was assessed using mixed-effect linear models. Additionally, a Random Forest Regressor was trained to evaluate the extent to which manual image grading of image quality could be replaced by automated assessment (inferred MOS). The results showed that ICC values were high for all QAF images, with slightly lower values in AMD-affected eyes. The average inter-day ICC was found to be 0.77 for QAF segments within the QAF8 ring and 0.74 for peripheral segments. Image quality was predicted with a mean absolute error of 0.27 on a 5-point scale, and of all evaluated reliability indices, MOS/inferred MOS proved most important. The findings suggest that QAF allows for reliable testing of autofluorescence levels at the posterior pole in patients with AMD in a multicenter, multioperator setting. Patient reliability indices could serve as eligibility criteria for clinical trials, helping identify patients with adequate retest reliability.

Figure 1

Color-coded QAF images from different AMD disease stages. Quantitative autofluorescence images (QAF) at baseline and 2-week follow-up from four study participants (male, 67 years, healthy eye; female, 69 years with early stage Age-Related Macular Degeneration (AMD); female, 75 years, intermediate AMD: male, 77 years late AMD, geographic atrophy). The color-coded images represent QAF levels. A color scale bar displaying AF level distribution is shown on the right (low QAF levels = black/blue, high QAF values = red-white). It appears that healthy and early AMD eyes have higher baseline QAF values than late disease stages of AMD. On visual inspection, same day QAF images (both columns left or right of the dashed line) appear to have a better color-coded reliability than between visits (columns compared across the dashed lines).

Figure 2

QAF image mean opinion score and predicted mean opinion score. (A) through (D) show quantitative autofluorescence (QAF) images of different quality. In the lower left corner, the Mean opinion scores (MOS) is displayed (human graders) and in the lower right the inferred Random-Forest Mean opinion score (RF-MOS) of QAF is reported. In QAF images with lower quality, the difference between MOS and RF-MOS increase. Opinion scores of QAF image quality took the following criteria into account: focus, illumination, symmetry, zoom, centering; all compiled by two readers.

Figure 3

Comparison of actual vs. random forest predicted image quality scores. The scatterplot visualizes the relationship between the actual mean opinion score (MOS) of image quality on the x-axis and the predicted MOS using the random forest algorithm on the y-axis. Each point on the scatterplot represents an image. If multiple data overlap, this results in a less transparent (or darker) blue, indicating a higher density of data at that location. A red line traverses the scatterplot, representing the linear regression model's fit to the data. The light red shaded region denotes the 95% confidence interval for the regression line.