Intereye Agreement of Retinopathy of Prematurity from Image Evaluation in the Telemedicine Approaches to Evaluating of Acute-Phase ROP (e-ROP) Study

Purpose To determine the symmetry on retinal image grading of fellow eyes for retinopathy of prematurity (ROP) features (stage, zone, and plus disease) and severity, to provide the basis for the within-subject comparison for ROP trials. Design Secondary analyses of data from the Telemedicine Approaches to Evaluating of Acute-Phase ROP (e-ROP) Study. Subjects Infants with birth weight less than 1251 g. Methods Infants underwent serial retinal imaging sessions in both eyes by certified imagers starting at 32 weeks' postmenstrual age. Two trained nonphysician readers graded each eye independently for ROP features in a 5-retinal-image set from each session. Discrepancies were adjudicated by a reading center supervisor. Readers were masked to all eye examination results, previous gradings of both eyes, current grading of the fellow eye, and demographic data. Main Outcome Measures The intereye agreement assessed using percentage exact agreement and weighted kappa (K_w) for stage, zone, plus, referral-warranted ROP (RW-ROP; defined as the presence of stage 3 or above, plus disease, or zone I ROP), and severity of ROP. Results Among 3918 imaging sessions in 1235 infants, the percent agreement (K_w) between paired eyes was 75.3% (0.65) for stage of ROP, 82.3% (0.68) for zone of ROP, 78.7% (0.51) for plus disease, 84.7% (0.56) for RW-ROP, and 72.7% (0.63) for severity of ROP. Similar intereye agreements were found when considering ROP features at the first imaging session, at the last imaging session, and at any imaging session. Based on image evaluations from all sessions, 412 infants (33.4%) had ROP stage 3 or above, 148 (12.0%) had zone I ROP, 70 (5.7%) had plus disease, and 419 (33.9%) had RW-ROP in 1 or both eyes; symmetrical findings were present in 71.4% for ROP stage 3 or above, 56.8% for zone I ROP, 50.0% for plus disease, and 73.7% for RW-ROP. Conclusions Image evaluations by masked, trained readers showed good intereye agreement in ROP characteristics, consistent with the high intereye agreement in ROP from clinical examinations by ophthalmologists in other studies. These data confirm that acute ROP is typically symmetrical and supports within-subject comparison in ROP trials.