Systemic effects of ophthalmic cyclopentolate on body weight in neonatal mice

Abstract

Background: Cyclopentolate is standardly used in ophthalmologic examinations of neonates to facilitate screening for retinopathy of prematurity. Reports of systemic effects have raised concerns of an increased risk of feeding intolerance after the examinations.

Objectives: The goal of this study was to evaluate systemic concentrations of cyclopentolate after ophthalmic administration, as well as assess changes in weight as an indirect measure of alteration in feeding.

Methods: Neonatal mice were randomized into three groups to simulate a neonatal model for ophthalmic medication administration. The cyclopentolate group received a one-time administration of tetracaine, cyclopentolate, and phenylephrine ophthalmologic solutions in accordance with the protocol used at the children's hospital. The placebo group received the same ophthalmic drop administration, except for normal saline in place of cyclopentolate, and the control group received no ophthalmic drops and minimal handling. Daily weights and serum samples to measure systemic concentrations of cyclopentolate post-ophthalmic administration were assessed at baseline and for 7 days following drop administration.

Results: Analysis of serum levels demonstrated detectability of systemic cyclopentolate after ophthalmic administration as early as 30 min (86 ng/ml), 1 h (60 ng/ml), and 24 h (6.2 ng/ml). There were also differences in weight gained on following ophthalmic administration observed between the cyclopentolate group and placebo group, with the cyclopentolate group weighing significantly less on days 3 and 7 (p = 0.02).

Conclusions: RESULTS indicate cyclopentolate is absorbed systemically and instillation of cyclopentolate decreases weight gain in neonatal mice compared to placebo. These preclinical findings provide rationale for further studies in neonatal patients.

Fig. 1.

Detection of cyclopentolate in serum post-ophthalmic administration. Cyclopentolate levels were detected in serum samples using LC/MS as described in the Methods and Materials. Samples were collected at 0.5 h, 1 h, 24 h, or 7 days after single-time ophthalmic administration. Results show that cyclopentolate was detected as early as 30–60 min after instillation and then levels gradually decreased over 24 h (n = 4–8).

Fig. 2.

Decreased weight gain in the cyclopentolate group compared to placebo and control groups. Mean weight of mice at baseline and 7 days after ophthalmic administration. Despite similar weights at baseline, mice in the control and placebo groups showed a tendency to have higher weight gain each day following drop administration compared to the cyclopentolate group, with statistically significant differences in weight seen on days 3 and 7 (* p < 0.05, n = 9 per group).