Purpose To identify patterns of interexpert discrepancy in plus disease diagnosis in retinopathy of prematurity (ROP). Design We developed 2 datasets of clinical images as part of the Imaging and Informatics in ROP study and determined a consensus reference standard diagnosis (RSD) for each image based on 3 independent image graders and the clinical examination results. We recruited 8 expert ROP clinicians to classify these images and compared the distribution of classifications between experts and the RSD. Participants Eight participating experts with more than 10 years of clinical ROP experience and more than 5 peer-reviewed ROP publications who analyzed images obtained during routine ROP screening in neonatal intensive care units. Methods Expert classification of images of plus disease in ROP. Main Outcome Measures Interexpert agreement (weighted κ statistic) and agreement and bias on ordinal classification between experts (analysis of variance [ANOVA]) and the RSD (percent agreement). Results There was variable interexpert agreement on diagnostic classifications between the 8 experts and the RSD (weighted κ, 0–0.75; mean, 0.30). The RSD agreement ranged from 80% to 94% for the dataset of 100 images and from 29% to 79% for the dataset of 34 images. However, when images were ranked in order of disease severity (by average expert classification), the pattern of expert classification revealed a consistent systematic bias for each expert consistent with unique cut points for the diagnosis of plus disease and preplus disease. The 2-way ANOVA model suggested a highly significant effect of both image and user on the average score (dataset A: P < 0.05 and adjusted R2 = 0.82; and dataset B: P < 0.05 and adjusted R2 = 0.6615). Conclusions There is wide variability in the classification of plus disease by ROP experts, which occurs because experts have different cut points for the amounts of vascular abnormality required for presence of plus and preplus disease. This has important implications for research, teaching, and patient care for ROP and suggests that a continuous ROP plus disease severity score may reflect more accurately the behavior of expert ROP clinicians and may better standardize classification in the future.
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