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.

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 Maori (95% CI no continuity correction -0.02 to 0.19). CONCLUSION: VLD microdrops enable safe and effective screening for ROPEE in both Maori and non-Maori preterm infants. TRIAL REGISTRATION NUMBER: ACTRN12619000795190.

Randomised controlled pilot trial comparing low dose and very low- dose microdrop administration of phenylephrine and cyclopentolate for retinopathy of prematurity eye examinations in neonates.

AIMS: To determine ifVery low dose mydriatic eye microdrop regimen sufficiently dilates the pupil (above 4.1 mm) compared with the currently used low dose mydriatic eye microdrop regimen.Cardiovascular, gastrointestinal and respiratory adverse effects occur following eye drop instillation. METHODS: Seventeen premature infants were recruited into this prospective, randomised controlled pilot trial in January 2017 to November 2018. Data were collected from the single-centre Neonatal Intensive Care Unit, Dunedin Hospital, New Zealand. The inclusion criteria were birth weight less than 1500 g or gestational age less than 31 weeks, or any premature infant requiring red reflex testing. Infants were randomised to receive either phenylephrine 1% or 0.5% and cyclopentolate 0.2% or 0.1%, 1 microdrop in both eyes. Efficacy outcome measures were pupil size at retinopathy of prematurity eye examination (ROPEE) and ophthalmologist rating of ease of screen. RESULTS: All participants had sufficient pupillary dilation for a successful ROPEE. Ophthalmologists rated the ROPEE as easy for 90% of all examinations. Pupil dilation measurements at the time of examination, mean±SD, 4.8±0.2 (95% CI 4.5 to 5.2) mm for treatment A and 5±0.2 (95%CI 4.6 to 5.4) mm for treatment B (p=0.61). There were no statistically significant differences between the groups for safety data. CONCLUSIONS: Very low dose microdrop administration of phenylephrine and cyclopentolate appears to be effective at sufficiently dilating the neonatal pupil for ROPEEs. Low dose and very low dose microdrop mydriatic regimens may also reduce the risk of unwanted adverse effects associated with these medicines. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (reference ACTRN12616001266459p).

Systematic review of mydriatics used for screening of retinopathy in premature infants.

INTRODUCTION: Routine retinopathy of prematurity eye examinations are an important part of neonatal care, and mydriatic medicines are essential in dilating the pupil for the eye examination. There are concerns about the level of evidence for efficacy and safety of these mydriatic medicines. OBJECTIVE: This review evaluates both efficacy and safety evidence of mydriatics used during the retinopathy of prematurity eye examination. METHOD: Systematic literature review. RESULTS: There is limited evidence guiding clinical practice for safety and efficacy of mydriatics. The majority of publications are underpowered and with an unclear to high level of bias. There are a wide variety of mydriatic regimens evaluated for efficacy and safety, and multiple regimens are associated with case reports. CONCLUSIONS: Current international guideline seems unnecessarily high, especially when the reviewed literature suggest that lower doses are effective, albiet from underpowered studies. The lowest effective combination regimen appears to be phenylephrine 1% and cyclopentolate 0.2% (1 drop). Microdrop administration of this regimen would further increase the safety profile, however, efficacy needs to be assessed.