Micro drops non-inferior to Standard drops for Retinopathy of Prematurity: JAMA

Retinopathy of prematurity (ROP) is one of the most significant risk factors in premature infants who are born prematurely as it can affect vision. Eyedrops that contain either adrenergic agonists, muscarinic antagonists, or their combination are used for adequate pupil dilation. However, they have the risk of causing systemic cardiorespiratory and gastrointestinal adverse events. Hence, researchers conducted a study to examine the noninferiority of micro drops of a combined mixture of 1.67% phenylephrine and 0.33% tropicamide compared to the standard eye drops.

A randomized, double-masked, noninferiority, crossover design trial was conducted on premature infants undergoing ROP screening at a tertiary center in Northern Greece from September 2021 to January 2023. 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 were considered eligible for the study. Random allocation was done to prescribe micro drops or standard drops of the diluted mixture with a 1-week washout period.

The horizontal pupil diameter at 45, 90, and 120 minutes was measured using a customized ruler in 0.5-mm increments. A predefined noninferiority margin of −0.4 mm was set. Parameters like 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. Hydrophilic liquid chromatography-tandem mass spectrometry measured Phenylephrine concentration in peripheral blood within 3 hours post-instillation.

Findings:

• About 83 infants were randomized with a mean [SD] gestational age of 29.7 [2.0] weeks and a mean [SD] birth weight of 1277 [374] g).
• Micro drops were superior for mydriatic efficacy at 45 minutes and non-inferior at 90 and 120 minutes.
• After standard drops, lower oxygen saturation levels at 45 and 90 minutes and a higher percentage of 24-hour hypertensive episodes were observed.
• A 1-compartment model with first-order absorption best described the pharmacokinetic data.

Thus, the researchers concluded that micro drops of combined 1.67% phenylephrine and 0.33% tropicamide in a mixture were proven superior regarding mydriatic efficacy at 45 minutes and non-inferior at 90 and 120 minutes compared with standard drops of the same regimen administered in infants undergoing ROP screening.

Micro drops were found to be safe, non-inferior to standard drops, and reduce system absorption. Due to their diagnostic efficacy, they can be preferable for ophthalmologists and neonatologists.

Further reading: Seliniotaki AK, Lithoxopoulou M, Virgiliou C, et al. Efficacy and Safety of Mydriatic Microdrops for Retinopathy of Prematurity Screening: The MyMiROPS Randomized Clinical Trial. JAMA Ophthalmol. Published online December 26, 2024. doi:10.1001/jamaophthalmol.2024.5462