To study the efficacy and safety of mydriatic microdrops compared with standard drops for retinopathy of prematurity (ROP) screening.
Preterm infants undergoing ROP screening received microdrops and standard drops of phenylephrine 1.67% and tropicamide 0.33% in a random allocation sequence at two consecutive weekly examinations. Primary outcome was pupil diameter measured by two masked observers at 45 (T45) and 90 (T90) minutes after instillation.
Twenty-five infants were randomized. No differences observed in mean pupil diameter after either administration technique at all time points (T45 Mean Difference: −0.14; 95% Confidence Interval: −0.38, 0.09; p = 0.23). Heart rate values at T120 were lower after microdrop instillation (p = 0.046). Otherwise, adverse events did not differ after either administration technique.
This pilot study provides evidence of microdrops mydriasis efficacy, while justifying a full-scale trial to confirm their non-inferiority compared with standard drops and provide more data about safety.
This is a preview of subscription content
Subscribe to Journal
Get full journal access for 1 year
only $8.25 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Hellström A, Smith LE, Dammann O. Retinopathy of prematurity. Lancet. 2013;382:1445–57.
Kremer LJ, Reith DM, Medlicott N, Broadbent R. Systematic review of mydriatics used for screening of retinopathy in premature infants. BMJ Paediatr Open. 2019;3:e000448.
Shell JW. Pharmacokinetics of topically applied ophthalmic drugs. Surv Ophthalmol. 1982;26:207–18.
Frangie JP. Clinical pharmacokinetics of various topical ophthalmic delivery systems. Clin Pharmacokinet. 1995;29:130–8.
Xue K, Hildebrand GD. Deep periocular infantile capillary hemangiomas responding to topical application of timolol maleate, 0.5%, drops. JAMA Ophthalmol. 2013;131:1246–8.
Alcorn J, McNamara PJ. Pharmacokinetics in the newborn. Adv Drug Deliv Rev. 2003;55:667–86.
Seliniotaki AK, Prousali E, Lithoxopoulou M, Kokkali S, Ziakas N, Soubasi V, et al. Alternative mydriasis techniques for retinopathy of prematurity screening. Int Ophthalmol. 2020;40:3613–9.
Lynch MG, Brown RH, Goode SM, Schoenwald RD, Chien DS. Reduction of phenylephrine drop size in infants achieves equal dilation with decreased systemic absorption. Arch Ophthalmol. 1987;105:1364–5.
Wheatcroft S, Sharma A, McAllister J. Reduction in mydriatic drop size in premature infants. Br J Ophthalmol. 1993;77:364–5.
Elibol O, Alçelik T, Yüksel N, Caglar Y. The influence of drop size of cyclopentolate, phenylephrine and tropicamide on pupil dilatation and systemic side effects in infants. Acta Ophthalmol Scand. 1997;75:178–80.
Eldridge SM, Chan CL, Campbell MJ, Bond CM, Hopewell S, Thabane L, et al. CONSORT 2010 statement: extension to randomised pilot and feasibility trials. BMJ. 2016;355:i5239.
Dwan K, Li T, Altman DG, Elbourne D. CONSORT 2010 statement: extension to randomised crossover trials. BMJ. 2019;366:l4378.
Mataftsi A, Moutzouri S, Karagianni P, Ziakas N, Soubasi V, Brazitikos P, et al. Retinopathy of prematurity occurrence and evaluation of screening policy in a large tertiary Greek cohort. Int Ophthalmol. 2020;40:385–91.
Dionne JM, Abitbol CL, Flynn JT. Hypertension in infancy: diagnosis, management and outcome. Pediatr Nephrol. 2012;27:17–32.
Flynn JT. Neonatal hypertension: diagnosis and management. Pediatr Nephrol. 2000;14:332–41.
Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg. 1978;187:1–7.
Whitehead AL, Julious SA, Cooper CL, Campbell MJ. Estimating the sample size for a pilot randomised trial to minimise the overall trial sample size for the external pilot and main trial for a continuous outcome variable. Stat Methods Med Res. 2016;25:1057–73.
Bland JM, Altman DG. Measuring agreement in method comparison studies. Stat Methods Med Res. 1999;8:135–60.
Kremer LJ, Broadbent R, Medlicott N, Sime MJ, McCaffrey F, Reith DM. 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. Arch Dis Child. 2021;106:603–8.
Mishima S, Gasset A, Klyce SD Jr, Baum JL. Determination of tear volume and tear flow. Invest Ophthalmol. 1966;5:264–76.
Walker J. Non-inferiority statistics and equivalence studies. BJA Educ. 2019;19:267–71.
Büyükcam A, Celik HT, Korkmaz A, Yurdakök M. Myoclonic seizure due to cyclopentolate eye drop in a preterm infant. Turk J Pediatr. 2012;54:419–20.
Poets CF. Apnea of prematurity: What can observational studies tell us about pathophysiology? Sleep Med. 2010;11:701–7.
Van Santvliet L, Ludwig A. Determinants of eye drop size. Surv Ophthalmol. 2004;49:197–213.
German EJ, Hurst MA, Wood D. Reliability of drop size from multi-dose eye drop bottles: is it cause for concern? Eye. 1999;13:93–100.
Craig EW, Griffiths PG. Effect on mydriasis of modifying the volume of phenylephrine drops. Br J Ophthalmol. 1991;75:222–3.
The authors declare no competing interests.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Seliniotaki, A.K., Lithoxopoulou, M., Talimtzi, P. et al. Efficacy and safety of mydriatic microdrops for retinopathy of prematurity screening: an external pilot crossover randomized controlled trial. J Perinatol (2021). https://doi.org/10.1038/s41372-021-01229-w