Abstract
<title>Abstract</title> <p>Background Pharmacologic mydriasis is essential for retinopathy of prematurity (ROP) screening; however, conventional ophthalmic drops substantially exceed neonatal tear film capacity, leading to systemic absorption and potential adverse effects. Microdrop administration may reduce drug exposure while preserving adequate pupillary dilation. This study aimed to determine whether microdrop administration of phenylephrine and tropicamide is noninferior to standard drops in achieving adequate mydriasis for ROP screening via a bottle adapter. Methods This single-center, randomized, parallel-group noninferiority trial was conducted in a tertiary neonatal unit in Chennai, India. Preterm infants undergoing routine ROP screening were randomized to receive either microdrops (10.26 µL) or standard drops (26.58 µL) of 2.5% phenylephrine and 0.8% tropicamide. Three doses were administered at 10-minute intervals. The primary outcome was the mean pupil diameter at 45 minutes after the first instillation. The secondary outcomes included physiological parameters (heart rate, oxygen saturation, and blood pressure), systemic and local adverse events, and the adequacy of ROP examination. A noninferiority margin of − 0.5 mm was prespecified. Results Among the 127 infants assessed for eligibility, 102 were randomized (microdrop group, n = 52; standard group, n = 50), and all completed the study. Baseline characteristics were comparable between the groups. The mean pupil diameter at 45 minutes was 6.54 ± 0.52 mm in the microdrop group and 6.38 ± 0.63 mm in the standard group (mean difference, 0.16 mm; 95% CI − 0.07–0.38), demonstrating noninferiority. Physiological parameters, including heart rate, oxygen saturation, and blood pressure, remained stable and comparable between the groups. Systemic adverse events were rare and similar across groups, and no local ocular complications were observed. ROP examination was successfully completed in all infants. Conclusion Microdrop administration of phenylephrine and tropicamide achieved mydriasis comparable to that of standard drops without increased adverse effects. This approach may represent a safer, clinically feasible and more physiologically appropriate strategy for ROP screening by reducing drug exposure in vulnerable preterm infants. Trial registration The study protocol was approved by the Institutional Ethics Committee of Madras Medical College, Chennai (IEC No. MMC/Approval/12052025). The trial was registered with the Clinical Trials Registry of India (CTRI/REF/2025/03/101681)on 10-03-2025.</p>