Abstract
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 1251g. METHODS: Infants underwent serial retinal imaging sessions in both eyes by certified imagers starting at 32-weeks postmenstrual age (PMA). Two trained non-physician 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 inter-eye agreement assessed using percent exact agreement and weighted kappa (K(w) ) for stage, zone, plus, referral-warranted ROP (RW-ROP, defined as presence of stage 3 or above, plus disease, or zone I ROP), and severity of ROP. RESULTS: Among 3918 image 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 inter-eye agreements were found when considering ROP features at the first image session, at the last image session, at any image session. Based on image evaluations from all sessions, 412 (33.4%) infants 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 one 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: Masked image evaluations by trained readers showed good inter-eye agreement in ROP characteristics, consistent with the high inter-eye 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.