urvival and neurodevelopmental outcomes in preterm infants, including periviable infants (22-25 weeks' gestational age), have improved over the past 20 years. However, despite these achievements, long-term neurodevelopmental outcomes for these infants remain a concern. [1][2][3] Prolonged exposure to early-life stress while in the intensive care nursery (ICN) causes alterations in the neural connectome leading to cognitive deficits later in life. [4][5][6] Stressors in the ICN include physiological stressors such as sepsis, environmental stressors such as excessive light, and experiential stressors such as blood draws. 4,7,8 Retinopathy of prematurity (ROP) examination by a trained ophthalmologist usually entails placement of an eyelid speculum, mydriatic drops, retinal illumination by the bright light of a binocular indirect ophthalmoscope, and pressure on the outer surface of the eye. 9 Binocular indirect ophthalmoscopy (BIO) is a repeated experiential stressor/ painful procedure for infants [10][11][12][13] and can produce changes in heart rate, both tachycardia and bradycardia, and apnea during and after examination. 11,14-16 Use of oral sucrose and intranasal fentanyl have been reported to reduce pain associated with retinal examination without increasing the risk of respiratory depression; however, their safety and efficacy need to be verified. 17,18 Approximately 70 000 infants per year in the United States receive 1 or more BIO examinations for ROP screening. 19IMPORTANCE Binocular indirect ophthalmoscopy (BIO) examination for retinopathy of prematurity (ROP) is a well-known cause of repeated preterm infant stress. OBJECTIVE To compare stress during investigational optical coherence tomography (OCT) imaging to that during BIO for ROP. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study examined infants at the bedside in the intensive care nursery. Consecutive preterm infants enrolled in Study of Eye Imaging in Preterm Infants (BabySTEPS) who had any research OCT imaging as part of the study. Patients were recruited from June to November 2019, and analysis began April 2020. MAIN OUTCOMES AND MEASURES Infant stress was measured using modified components of a neonatal pain assessment tool before (baseline) and during OCT imaging and BIO examination of each eye. RESULTS For 71 eye examinations of 16 infants (mean [SD] gestational age, 27 [3] weeks; birth weight, 869 [277] g), change from baseline to each eye examination was lower during OCT imaging than during BIO and the difference between OCT imaging and BIO at each eye examination was significant for the following: infant cry score (first eye examination: mean [SD], 0.03 [0.