The Little Eye Drop Study: a randomised controlled non-inferiority trial on the microdrop administration of phenylephrine and cyclopentolate eye drops in neonates

Our study aims to find out if low dose vs very low dose pupil dilating eye microdrops are effective in premature infants, and if the eye drops are associated with a low risk of harm. Retinopathy of prematurity (ROP) is a major cause of blindness in children who were born before 31 weeks gestational age or with a birth weight less than 1250 g. Because of the risk of permanent blindness, this group of premature infants have routine ROP eye examinations (ROPEE). The eye examination involves a two-step process; 1) administration of mydriatic (pupil dilating) eye drops, and 2) the eye examination. The eye drops are administered approximately 30 to 60 minutes prior to the ROPEE, and the eye exam occurs fortnightly, however if there are signs of retinopathy, the infant is likely to need weekly eye checks. Sufficient pupil dilation is needed to view of the retina. Phenylephrine with cyclopentolate or tropicamide are the eye drop regimens that are used to dilate the pupil. We know from our recent survey of neonatal units in Australia and New Zealand, that there is a wide variety of these regimens in use. Regimens varied in concentration, drop volume and frequency of administration, and within this variation, 5 of the 11 centres were using adult doses, 2 were using more than an adult dose, and only 4 were using less than adult doses. Results from a systematic review of the literature suggested that low dose mydriatics are effective at sufficiently dilating the neonatal pupil for ROPEEs.1 Mydriatics have been associated with clinically significant cardiovascular, respiratory, and gastrointestinal adverse effects.1 Therefore, guidance on clinical practice is required to help reduce the exposure of excessive doses that some premature infants are receiving, especially when there is evidence that low doses are effective. References 1. Kremer LJ RD, Medlicott N, Broadbenr R. Systematic review of mydriatics used for screening of retinopathy in premature infants. BMJ Paediatrics Open 2019 doi: doi:10.1136/bmjpo-2019-000448