Interreader and Intermodality Variability in Macular Atrophy Quantification in Neovascular Age-related Macular Degeneration: Comparison of 6 Imaging Modalities

Abstract

Macular atrophy is a common complication in neovascular age-related macular degeneration (AMD) and is associated with poorer visual outcomes. This study evaluated interreader and intermodality variability in measuring macular atrophy in previously treated neovascular AMD eyes without exudation using 6 imaging modalities. Prospective, cohort study. Thirty participants with previously treated neovascular AMD showing no signs of exudation at the time of enrollment and exhibiting macular atrophy. During the same clinic visit, patients were imaged using 6 different imaging modalities: color fundus photography (CFP; Clarus, Carl Zeiss Meditec), near-infrared imaging (NIR; Spectralis, Heidelberg Engineering), structural OCT (Spectralis, Heidelberg Engineering), green fundus autofluorescence (GAF; Clarus, Carl Zeiss Meditec), blue fundus autofluorescence (BAF; Spectralis, Heidelberg Engineering), and pseudocolor imaging (MultiColor; Spectralis, Heidelberg Engineering). Two readers independently measured the macular atrophy area. Interreader and intermodality agreement. The 95% coefficient of repeatability was 5.98 mm2 for CFP, 4.46 mm2 for MultiColor, 3.90 mm2 for BAF, 3.92 mm2 for GAF, 4.86 mm2 for NIR, and 3.55 mm2 for OCT. Similarly, the coefficient of variation was lowest for OCT-based grading at 0.08 and highest for NIR-based grading at 0.28. Accordingly, the intraclass correlation coefficient was 0.742 for CFP, 0.805 for MultiColor, 0.857 for BAF, 0.850 for GAF, 0.755 for NIR, and 0.917 for OCT. The 6 different imaging modalities presented measurements with different mean values, with only a limited number of comparisons not significantly different between the instruments, although measurements were correlated. The largest size of macular atrophy was measured with structural OCT-based grading (median= 4.65 mm2; interquartile range [IQR]= 4.78 mm2) and the smallest was with CFP-based grading (median= 3.86 mm2; IQR= 5.06 mm2). Inconsistencies arose from various factors. In patients with neovascular AMD, macular atrophy measurements vary significantly depending on the imaging technique used. Color fundus photography-based assessments yielded the smallest macular atrophy sizes, whereas structural OCT-based assessments produced the largest. These discrepancies stem from both the inherent limitations of each modality in assessing retinal pigment epithelial atrophy and factors related to neovascularization, such as the coexistence of fibrosis. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.