To validate the FIRST-ROP algorithm in a medium-risk cohort of infants undergoing screening for retinopathy of prematurity (ROP).

Retrospective diagnostic comparison.

Infants who did not meet criteria for microprematurity or nanoprematurity (gestational age ≥ 27 weeks and birth weight ≥ 800 g) were included. Outcomes assessed included rates of ROP diagnosis and treatment-warranted ROP (TW-ROP), as well as postmenstrual age (PMA) at first diagnosis and initiation of treatment. Paired binary detection outcomes between traditional ROP screening strategies and the FIRST-ROP algorithm, which defers screening until 34 weeks PMA, were compared using the McNemar test.

Among 8564 infants screened, 3641 (36%) met inclusion criteria, of whom 604 (17%) developed ROP. Median PMA at first ROP diagnosis was 35.1 weeks (interquartile range [IQR], 34.0-36.6 weeks; range, 31.3-51.4 weeks). Median PMA at stage 3 diagnosis was 35.6 weeks (IQR, 34.0-37.0 weeks; range, 32.3-47.6 weeks). Median PMA at first treatment was 40.0 weeks (IQR, 37.1-41.4 weeks; range, 34.3-44.4 weeks). Fifteen infants (2%) required treatment, of whom 10 (67%) had type 1 ROP. Initiating screening at 34 weeks PMA significantly reduced examinations compared with standard screening ( P < .001), corresponding to an estimated 17% fewer visits per patient. No cases of TW-ROP would have been missed under the FIRST-ROP strategy (95% CI, 99.3%-100%).

Over 3 decades, no infants in this medium-risk cohort required treatment before 34 weeks PMA. These findings validate the FIRST-ROP algorithm and support safe deferral of the initial ROP examination to 34 weeks PMA, reducing screening burden while maintaining sensitivity for TW-ROP.