Efficacy and Safety of Cyclopentolate Microdrops for Cycloplegic Refraction in Children

Efficacy and Safety of Cyclopentolate Microdrops for Cycloplegic Refraction in Children: a Non-inferiority Crossover Randomized Controlled Trial

The purpose is to test the hypothesis that microdrop instillation of cyclopentolate 1% is non-inferior to standard of care, i.e., standard drop instillation of cyclopentolate 1%. Comparison, also, will be made to the subsequent adverse events.

Study Overview

• Status: Completed
• Conditions: Cycloplegic Refraction
• Intervention / Treatment: Device: Microdrop instillation of cyclopentolate 1%; Device: Standard drop instillation of cyclopentolate 1%

Detailed Description

A non-inferiority, crossover, randomized controlled trial will be conducted for this purpose. Participants will be randomly assigned to receive either a) microdrops on their first and standard drops on their second screening examination a week later (M/S group), or b) standard drops first and microdrops a week later (S/M group). Microdrops will be instilled using the Nanodropper® device, while standard drops will be instilled directly through the commercially available plastic multidose mydriatic dropper bottle. For all participants, the eyedrop will be firstly instilled in the right eye and this will be the eye that will be used for the analyses. Written informed consent will be obtained from the parents/guardians for the children's enrollment.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 4

Contacts and Locations

Study Locations

• Greece
  • Thessaloniki, Greece
    • Papageorgiou General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Children aged 4-16 years old, who require cycloplegic refraction measurements in the context of regular ophthalmological examination as outpatients in the 2nd Department of Ophthalmology of AUTh at a tertiary center in Northern Greece.

Exclusion Criteria:

1. Inability for the child to cooperate with autorefractometer
2. Difficulties for the family to attend the follow-up visit
3. Known allergic reaction to cyclopentolate or to any of the other ingredients of this solution
4. Presence of any contraindication for the child to receive cyclopentolate eyedrops (e.g. neurological disease of concern)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study Group; Cycloplegia with microdrops	Device: Microdrop instillation of cyclopentolate 1%; 1 drop administered through the Nanodropper device adapted to the commercially available multi-dose dropper bottle
Active Comparator: Control Group; Cycloplegia with standard drops	Device: Standard drop instillation of cyclopentolate 1%; 1 drop administered directly through the commercially available multi-dose dropper bottle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cycloplegic refraction: diopters of spherical equivalent	The difference in spherical equivalent (SE) after microdrop and standard drop instillation (cycloplegic efficacy)	40 minutes post-instillation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate: bpm	The difference in heart rate after microdrop and standard drop instillation (safety outcome)	40 minutes post-instillation
Flushing: absent, minor, major	The difference in the number of patients who experience flushing after microdrop and after standard drop instillation (safety outcome)	40 minutes post-instillation
Behavioral changes: yes or no	The difference in the number of patients who experience behavioral changes after microdrop and after standard drop instillation (safety outcome)	40 minutes post-instillation
Sleepiness: yes or no	The difference in the number of patients who experience sleepiness after microdrop and standard drop instillation (safety outcome)	40 minutes post-instillation

Collaborators and Investigators

• Sponsor: Aristotle University Of Thessaloniki
• Collaborators: Nanodropper, Inc.

Publications and helpful links

General Publications

• Hoppe CB, Yonamine S, Kao BW, Turner ML, Ou Y, Han Y, Keenan JD, Oatts JT. Randomized Trial to Evaluate the Efficacy of the Nanodropper Device for Pupillary Dilation and Cycloplegia in Children. Ophthalmology. 2023 Mar;130(3):324-330. doi: 10.1016/j.ophtha.2022.10.016. Epub 2022 Oct 22.
• Noske W. Cycloplegic refraction using atropine minidrops. Strabismus. 1993;1(1):17-23. doi: 10.3109/09273979309033849.
• Seliniotaki AK, Tziola T, Lithoxopoulou M, Tzamalis A, Ziakas N, Mataftsi A. Optimizing instilled drug delivery: a scoping review of microdrops in ophthalmology. Graefes Arch Clin Exp Ophthalmol. 2025 Jul;263(7):1765-1787. doi: 10.1007/s00417-025-06773-1. Epub 2025 Feb 26.

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2024
• Primary Completion (Actual): September 26, 2025
• Study Completion (Actual): October 8, 2025

Study Registration Dates

• First Submitted: March 14, 2025
• First Submitted That Met QC Criteria: March 14, 2025
• First Posted (Actual): March 20, 2025

Study Record Updates

• Last Update Posted (Estimated): November 4, 2025
• Last Update Submitted That Met QC Criteria: November 3, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: children; cycloplegia; cyclopentolate; refraction; microdrops
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Parasympatholytics; Mydriatics; Cyclopentolate
• Other Study ID Numbers: 383/19-06-2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes