A Study Investigating Whether Low Dose Eyedrops for Pupil Dilation is as Effective and Safe as Standard Dose Eyedrops in Examination for Retinopathy of Prematurity.

Randomized Controlled Trial Comparing the Efficacy and Safety of Mydriatic Microdrops Over Standard Dose Mydriatics for Pupil Dilation in Retinopathy of Prematurity Examination

A prospective, randomized controlled study was conducted from August, 2022 to March, 2023 in the neonatal intensive care unit in Queen Mary Hospital, Hong Kong. The aim of this study was to determine whether microdrops Mydrin-P demonstrates similar efficacy as standard Mydrin -P eyedrops applied to neonates undergoing retinopathy of prematurity (ROP) screening exams, also to ascertain the optimal time for eye examination after administration of mydriatics and assess whether the cardiovascular, respiratory and gastrointestinal adverse effects differ between microdrops and standard dose Mydrin-P.

Preterm infants were randomized to receive either the standard Mydrin-P eyedrops or the mydriatic microdrops which contained around one-third of the standard Mydrin-P dosage. The primary outcome measured whether a successful ROP examination was conducted. Secondary outcomes included pupil diameters at baselines, 30 minutes, 60 minutes, 120 minutes after eyedrops instillation and at the time of ROP exam as well as adverse effects followed by the mydriatics administration.

A total of 18 patients were enrolled in this study with total 46 episodes of ROP recorded. All episodes with microdrops instillation led to successful ROP exams. There was no statistically significant difference between standard eyedrops and microdrops in determining the success of ROP exam (p=0.233). Mean pupil diameter did not differ between the microdrops and standard eyedrops group. At the time of ROP exam, the mean pupil diameter was 5.47mm in the standard eyedrops group and 5.73mm in the microdrops group. The optimal time for ROP exam was 60 minutes to 120 minutes after first dose of mydriatic. Also there was no difference in the occurrence of systemic side effects when compared to standard Mydrin P drops.

Hence the study concluded that microdrops have similar efficacy and safety profile compared to standard Mydrin-P eyedrops.

Study Overview

• Status: Completed
• Conditions: Retinopathy of Prematurity
• Intervention / Treatment: Drug: Standard Mydrin-P; Drug: Microdrop Mydrin-P

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Neonates with estimated gestational age (EGA) at birth ≤32 weeks
• Neonates with birth weight ≤1500g

Exclusion Criteria:

• Neonates with severe clinical condition with unstable vital signs
• Neonates with congenital anomalies, syndromic disease
• Neonates with ophthalmological conditions such as eye infections, congenital eye anomalies, trauma
• Neonates with conditions that are contraindicated to mydriatic use

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Standard Mydrin-P Group; Subjects allocated to the Standard Mydrin P group will receive standard Mydrin-P (0.5% tropicamide / 0.5% phenylephrine HCl) which is the standard eyedrops used for dilation of pupil before retinopathy of prematurity examination.	Drug: Standard Mydrin-P; Standard Mydrin-P is the standard mydriatic used for retinopathy of prematurity exam as per our local usual practice.
Experimental: Microdrop group; Those allocated to the microdrop group will receive microdrop Mydrin-P for pupil dilation before retinopathy of prematurity exam.	Drug: Microdrop Mydrin-P; Microdrop Mydrin-P consists of around one third of the standard Mydrin-P drop size. Drop volume measurement was performed using a precision weight scale (Sartorius) with accuracy up to 0.001g. The microdrop administration was conducted via attachment of a 16 gauge needle to a 1ml syringe.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Successfulness of a ROP exam	Primary outcome of the study was whether the ROP screening was successfully performed or not without additional eyedrops defined by the ophthalmologist conducting the exam.	From the start of pupil dilation to pupil examination which is around 2 to 3 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pupil diameters	Pupil diameter (in millimetres, mm) was documented at baseline (before eyedrops are applied, T0), 30 minutes from first dose of eyedrop (T30), 60 minutes from first dose of eyedrop (T60), 120 minutes from first dose of eyedrop (T120) and at time of ROP exam (TROP). Two measurements were taken during each time, one by visual assessment, another one by pupillometer measurement.	From start of pupil dilation (baseline) to 120 minutes after pupil dilation, total time is 120 minutes.
Heart rate	Heart rate at baseline (before eyedrops are applied, T0), 30 minutes from first dose of eyedrop (T30), 60 minutes from first dose of eyedrop (T60), 120 minutes from first dose of eyedrop (T120) and at time of ROP exam (TROP) were captured.	From start of pupil dilation (baseline) to 120 minutes after pupil dilation, total time is 120 minutes.
Blood pressure	Blood pressure at baseline (before eyedrops are applied, T0), 30 minutes from first dose of eyedrop (T30), 60 minutes from first dose of eyedrop (T60), 120 minutes from first dose of eyedrop (T120) and at time of ROP exam (TROP) were captured.	From start of pupil dilation (baseline) to 120 minutes after pupil dilation, total time is 120 minutes.
Oxygen saturation	Oxygen saturation at baseline (before eyedrops are applied, T0), 30 minutes from first dose of eyedrop (T30), 60 minutes from first dose of eyedrop (T60), 120 minutes from first dose of eyedrop (T120) and at time of ROP exam (TROP) were captured.	From start of pupil dilation (baseline) to 120 minutes after pupil dilation, total time is 120 minutes.
Oxygen requirement	Oxygen requirement at baseline (before eyedrops are applied, T0), 30 minutes from first dose of eyedrop (T30), 60 minutes from first dose of eyedrop (T60), 120 minutes from first dose of eyedrop (T120) and at time of ROP exam (TROP) were captured.	From start of pupil dilation (baseline) to 120 minutes after pupil dilation, total time is 120 minutes.
Episodes of vomiting	Episodes of vomiting were documented in the 24 hours after eyedrops administration and compared to the baseline which is the past 24 hours prior to the eyedrops exposure	From start of pupil dilation (baseline) to 24 hours after pupil dilation, total time is 24 hours.
Volume of gastric residuals	Volume of gastric residuals were documented in the 24 hours after eyedrops administration and compared to the baseline which is the past 24 hours prior to the eyedrops exposure	From start of pupil dilation (baseline) to 24 hours after pupil dilation, total time is 24 hours.
Episodes of apnoea	Episodes of apnoea were documented in the 24 hours after eyedrops administration and compared to the baseline which is the past 24 hours prior to the eyedrops exposure	From start of pupil dilation (baseline) to 24 hours after pupil dilation, total time is 24 hours.
Episodes of periorbital blanching	Episodes of periorbital blanching were documented in the 24 hours after eyedrops administration and compared to the baseline which is the past 24 hours prior to the eyedrops exposure	From start of pupil dilation (baseline) to 24 hours after pupil dilation, total time is 24 hours.

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Investigators: Study Chair: Khair Jalal, Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2022
• Primary Completion (Actual): March 22, 2023
• Study Completion (Actual): March 22, 2023

Study Registration Dates

• First Submitted: February 18, 2024
• First Submitted That Met QC Criteria: February 24, 2024
• First Posted (Estimated): March 1, 2024

Study Record Updates

• Last Update Posted (Estimated): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 24, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Preterm; Microdrops; Retinopathy of prematurity; Mydriatics; Retinopathy of prematurity screening; Mydrin P
• Additional Relevant MeSH Terms: Eye Diseases; Infant, Newborn, Diseases; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Infant, Premature, Diseases; Pupil Disorders; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Retinal Diseases; Premature Birth; Retinopathy of Prematurity; Mydriasis
• Other Study ID Numbers: UW22221

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No