Systemic Absorption of Cyclopentolate and Adverse Events After Retinopathy of Prematurity Exams

Abstract

Purpose Preterm infants undergoing Retinopathy of Prematurity Eye Exams (ROPEE) may experience adverse events, possibly from systemic absorption of cyclopentolate. The purpose of this study was to analyze the association between adverse events and drug levels found in neonates undergoing ROPEE. Materials and Methods 25 infants were randomized into two groups during routine ROP screening: 5 infants for blood collection before mydriatic drops and 20 for blood collection 1 h after eye drops. Blood was collected onto dried blood spot cards, extracted, and analyzed for cyclopentolate and phenylephrine using liquid chromatography and mass spectrometry. Relationships between drug levels and adverse events were assessed. Results Cyclopentolate (range 6–53 ng/ml) was observed in 15 of 18 infants, while phenylephrine was not detected. Levels of cyclopentolate were significantly higher in infants who were on oxygen (p = 0.01). There was a significant association between cyclopentolate levels and gastric residuals in tube-fed infants not receiving oxygen (p = 0.01). Conclusions Cyclopentolate levels varied among preterm infants after ROPEE. Cyclopentolate was positively associated with increased gastric residuals. Underlying medical conditions requiring oxygen administration may affect absorption and metabolism of cyclopentolate. There is a need to predict infants at risk for high blood levels of cyclopentolate in order to prevent or treat adverse events after ROPEE.

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

“…Cyclopentolate serum concentrations were measured following cyclopentolate 0.2% (3 d) administration 28. Results show that infants who were receiving oxygen therapy, had significantly higher cyclopentolate concentrations, than infants who were not receiving oxygen therapy (p=0.01).…”

“…15 This is compared with a RCT (n=25), where gastric residuals increased following phenylephrine 1% and cyclopentolate 0.2% (3 d) administration (p=0.01) (table 6). 28…”

Ocular Refraction at Birth and Its Development During the First Year of Life in a Large Cohort of Babies in a Single Center in Northern Italy

“…Although cyclopentolate 0.5% is a better cycloplegic agent than tropicamide (1%) and has been used in other studies (40), it also produces systemic and local adverse events due to its muscarinic antagonist activity (41). For this reason, we chose to use tropicamide in our study.…”

Ophthalmic Insert versus Eye Drops for Mydriasis in Neonates: A Randomized Clinical Trial

“…However, adverse events remain a concern [8], especially for cyclopentolate, which is contraindicated for children under 1 year of age in several European countries because of possible severe central nervous system side effects. The insert appeared to be well tolerated.…”

“…However, in premature infants this can be difficult to achieve due to the immaturity of the iris sphincter [3], and frequently requires repeated topical instillations of mydriatic agents. While relatively innocuous in adults, mydriatic agents can lead to systemic side effects, such as cardiovascular complications in infants, as a large proportion of the eye drop volume may be absorbed from the conjunctival and nasal mucosa [4-8]. Several studies have evaluated mydriatic regimens for preterm infants [9-12].…”