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Updated: Jul 15, 2026
Transcutaneous Microcirculatory Imaging in Preterm Neonates
Published on: December 31, 2015
Efficacy and Safety of Mydriatic Microdrops for Retinopathy of Prematurity Screening: The MyMiROPS Randomized
Aikaterini K Seliniotaki1,2, Maria Lithoxopoulou3, Christina Virgiliou4
1Second Department of Ophthalmology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Papageorgiou General Hospital, Thessaloniki, Greece.
Importance:
Commercial mydriatics administered in preterm infants during retinopathy of prematurity (ROP) screening have been associated with various cardiorespiratory and gastrointestinal adverse events.
Objective:
To examine whether microdrops of a combined mixture of 1.67% phenylephrine and 0.33% tropicamide are noninferior to standard drops regarding mydriatic efficacy at 45, 90, and 120 minutes. The occurrence of systemic adverse events and systemic absorption of phenylephrine eyedrops were additional secondary outcomes.
Design, Setting, And Participants:
This randomized clinical trial with a double-masked, noninferiority, crossover design included infants undergoing ROP screening at a tertiary center in Northern Greece from September 2021 to January 2023. Eligible participants were infants with gestational age below 32 weeks and/or birthweight under 1501 g, or infants beyond these thresholds referred by an attending neonatologist due to comorbidities.
Interventions:
Either microdrops or standard drops of the diluted mixture were administered at a random allocation sequence with a 1-week washout period.
Main Outcomes And Measures:
The horizontal pupil diameter at 45, 90, and 120 minutes was measured using a customized ruler in 0.5-mm increments. Mixed-effects linear regression models were developed, and the confidence interval (CI) approach was used for assessing noninferiority. The predefined noninferiority margin was -0.4 mm. Heart rate; oxygen saturation; blood pressure measurements at 45, 90, and 120 minutes; 24-hour hypertensive episodes; and 48-hour systemic adverse events were assessed. Phenylephrine concentration in peripheral blood within 3 hours postinstillation was measured using hydrophilic liquid chromatography-tandem mass spectrometry. Pooled pharmacokinetic parameters were calculated based on a developed mathematical model.
Results:
A total of 83 infants were randomized (mean [SD] gestational age, 29.7 [2.0] weeks; mean [SD] birth weight, 1277 [374] g). Microdrops proved to be superior regarding mydriatic efficacy at 45 minutes (mean difference, 0.12; Bonferroni-corrected 95% CI, 0.01 to 0.23; P = .008) and noninferior at 90 minutes (Bonferroni-corrected 95% CI, -0.10 to 0.17) and 120 minutes (Bonferroni-corrected 95% CI, -0.18 to 0.14). Lower levels of oxygen saturation at 45 minutes (mean difference, 0.66; 95% CI, 0.09 to 1.24; P = .03) and 90 minutes (mean difference, 0.58; 95% CI, 0.03 to 1.14; P = .04) and higher percentage of 24-hour hypertensive episodes (median [IQR] percentage of hypertensive episodes: microdrops, 0.10% [0.02%-0.19%] vs standard drops, 0.14% [0.06%-0.40%]; P = .01) were observed after standard drops. A 1-compartment model with first-order absorption best described the pharmacokinetic data.
Conclusion And Relevance:
To our knowledge, this is the first study establishing noninferiority of microdrops compared with standard drops of a diluted mydriatic mixture, showing reduced systemic adverse events after microdrops and determining the pharmacokinetic profile of phenylephrine eyedrops in preterm infants.
Trial Registration:
ClinicalTrials.gov Identifier: NCT05043077.
Insights
Microdoses of phenylephrine and tropicamide eye drops are as effective as standard doses for retinopathy of prematurity screening in preterm infants. This method also showed fewer adverse events, improving safety for vulnerable infants.
Area of Science:
- Ophthalmology
- Neonatology
- Clinical Pharmacology
Background:
- Commercial mydriatics used in retinopathy of prematurity (ROP) screening in preterm infants are linked to cardiorespiratory and gastrointestinal adverse events.
- Developing safer and effective mydriatic protocols is crucial for ROP screening in preterm infants.
Purpose of the Study:
- To evaluate the noninferiority of microdoses versus standard doses of a phenylephrine and tropicamide mixture for mydriatic efficacy in preterm infants undergoing ROP screening.
- To assess systemic adverse events and phenylephrine absorption associated with microdose versus standard-dose mydriatics.
Main Methods:
- A randomized, double-masked, noninferiority, crossover trial involving preterm infants undergoing ROP screening.
- Comparison of microdoses vs. standard drops of a 1.67% phenylephrine/0.33% tropicamide mixture, with a 1-week washout period.
- Assessment of pupil diameter, heart rate, oxygen saturation, blood pressure, hypertensive episodes, and phenylephrine pharmacokinetics.
Main Results:
- Microdoses demonstrated noninferior mydriatic efficacy at 90 and 120 minutes and were superior at 45 minutes compared to standard drops.
- Standard drops were associated with lower oxygen saturation and a higher percentage of hypertensive episodes.
- Pharmacokinetic analysis indicated a 1-compartment model with first-order absorption for phenylephrine.
Conclusions:
- Microdoses of phenylephrine and tropicamide are noninferior to standard doses for ROP screening in preterm infants.
- The microdose approach reduces systemic adverse events, enhancing safety.
- This study establishes the noninferiority and safety profile of mydriatic microdoses in this population.
