Low dose or very low dose phenylephrine and cyclopentolate microdrops for retinopathy of prematurity eye examinations (The Little Eye Drop Study): a randomised controlled non-inferiority trial

Arch Dis Child Fetal Neonatal Ed. 2023 Jul;108(4):380-386. doi: 10.1136/archdischild-2022-324929. Epub 2023 Jan 2.

Abstract

Objective: To determine if very low dose (VLD, 0.5% phenylephrine, 0.1% cyclopentolate) mydriatic microdrop (approximately 7 μL) administration (up to three doses) is non-inferior to low dose (LD, 1% phenylephrine, 0.2% cyclopentolate) mydriatic microdrop administration for ophthalmologist-determined successful retinopathy of prematurity eye examination (ROPEE).

Design: Multicentre, prospective, randomised controlled, non-inferiority clinical trial.

Setting: Four neonatal intensive care units in Aotearoa, New Zealand from October 2019 to September 2021.

Patients: Infants with a birth weight less than 1250 g or gestational age less than 30+6 weeks and who required a ROPEE.

Interventions: The intervention: microdrop (approximately 7 μL) of VLD (0.5% phenylephrine and 0.1% cyclopentolate) to both eyes, or the comparison: microdrop of LD (1% phenylephrine and 0.2% cyclopentolate) to both eyes. Up to three doses could be administered.

Main outcome measures: The primary outcome measure was an ophthalmologist-determined successful ROPEE.

Results: One hundred and fifty preterm infants (LD mean GA=27.4±1.8 weeks, mean birth weight=1011±290 g, VLD mean GA=27.5±1.9 weeks, mean birth weight=1049±281 g,) were randomised. Non-inferiority for successful ROPEE was demonstrated for the VLD group compared with the LD group (VLD successful ROPEE=100%, LD successful ROPEE=100%, 95% CI no continuity correction -0.05 to 0.05) and for Māori (95% CI no continuity correction -0.02 to 0.19).

Conclusion: VLD microdrops enable safe and effective screening for ROPEE in both Māori and non-Māori preterm infants.

Trial registration number: ACTRN12619000795190.

Keywords: intensive care units, neonatal; neonatology; ophthalmology; pharmacology; therapeutics.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Birth Weight
  • Cyclopentolate* / pharmacology
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Premature
  • Infant, Very Low Birth Weight
  • Mydriatics / pharmacology
  • Ophthalmic Solutions / pharmacology
  • Phenylephrine / pharmacology
  • Prospective Studies
  • Pupil
  • Retinopathy of Prematurity* / diagnosis
  • Retinopathy of Prematurity* / drug therapy

Substances

  • Cyclopentolate
  • Mydriatics
  • Phenylephrine
  • Ophthalmic Solutions