Efficacy and Safety of Mydriatic Microdrops Compared With Standard Drops for Retinopathy of Prematurity (ROP) Screening: a Pilot Randomized Clinical Trial

Study Overview
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Brief Summary
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The purpose is to assess whether the use of microdrop instillation of phenylephrine 1.67% and tropicamide 0.33% maintains mydriatic efficacy while presents an improved safety profile compared with standard drops of phenylephrine 1.67% and tropicamide 0.33%, which is routine care for pupil dilation during retinopathy of prematurity (ROP) screening in our neonatal intensive care unit.

Detailed Description
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A pilot prospective randomized crossover clinical trial is conducted for assessing the mydriatic efficacy and safety of microdrops (6-7 μL) compared with standard drops (28-34 μL) for retinopathy of prematurity screening. A random number table was used to allocate participants into either a) receiving standard drop on their first and microdrop on their second screening examination a week later, or b) receiving microdrop first and standard drop a week later. The mydriatic agent contains phenylephrine 1.67% and tropicamide 0.33%, which derives from compounding the commercial phenylephrine 5% with the commercial tropicamide 0.5% in volume ratio 1:2.

Official Title
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Efficacy and Safety of Mydriatic Microdrops Compared With Standard Drops for Retinopathy of Prematurity (ROP) Screening: a Pilot Randomized Clinical Trial

Conditions
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Retinopathy of Prematurity

Intervention / Treatment
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* Drug: Microdrop administration [phenylephrine 1.67% + tropicamide 0.33% (drop volume: 6-7 μL)]
* Drug: Standard drop administration [phenylephrine 1.67% + tropicamide 0.33% (drop volume: 28-34 μL)]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Preterm infants undergoing screening for ROP, i.e. with gestational age (GA) < 32 weeks and/or birth weight (BW) < 1501 grams infants of greater GA and BW with increased comorbidity, e.g. sepsis, prolonged need for oxygen supplementation etc. Exclusion Criteria: Unstable clinical condition Suspicion of cardiovascular disease Severe congenital anomalies Clinical syndromes Traumatic apoptosis of the corneal epithelium Corneal ulcer Anatomical variations of the anterior segment

Ages Eligible for Study
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Minimum Age: 30 Weeks
Maximum Age: 37 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Group<br>Mydriasis with microdrops | Drug: Microdrop administration [phenylephrine 1.67% + tropicamide 0.33% (drop volume: 6-7 μL)]<br>* 1 drop (6-7 μL) for 3 doses, 5 minutes' intervals<br>|
| Active Comparator: Control Group<br>Mydriasis with standard drops | Drug: Standard drop administration [phenylephrine 1.67% + tropicamide 0.33% (drop volume: 28-34 μL)]<br>* 1 drop (28-34 μL) for 3 doses, 5 minutes' intervals<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mydriatic efficacy: mm of pupil diameter (left and right eye) |  | 45 minutes after the first drop instillation | 
| Mydriatic efficacy: mm of pupil diameter (left and right eye) |  | 90 minutes after the first drop instillation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mydriatic efficacy: mm of pupil diameter (left and right eye) |  | 120 minutes after the first drop instillation | 
| Systemic side effects: measurements of Heart Rate (bpm) |  | 45 minutes after the first drop instillation | 
| Systemic side effects: measurements of Heart Rate (bpm) |  | 90 minutes after the first drop instillation | 
| Systemic side effects: measurements of Heart Rate (bpm) |  | 120 minutes after the first drop instillation | 
| Systemic side effects: measurements of oxygen saturation (SpO2) (%) |  | 45 minutes after the first drop instillation | 
| Systemic side effects: measurements of oxygen saturation (SpO2) (%) |  | 90 minutes after the first drop instillation | 
| Systemic side effects: measurements of oxygen saturation (SpO2) (%) |  | 120 minutes after the first drop instillation | 
| Systemic side effects: measurements of Blood Pressure (Systolic, Diastolic and Mean Blood Pressure) (mmHg) |  | 45 minutes after the first drop instillation | 
| Systemic side effects: measurements of Blood Pressure (Systolic, Diastolic and Mean Blood Pressure) (mmHg) |  | 90 minutes after the first drop instillation | 
| Systemic side effects: measurements of Blood Pressure (Systolic, Diastolic and Mean Blood Pressure) (mmHg) |  | 120 minutes after the first drop instillation | 
| Systemic side effects: measurements of Blood Pressure (Systolic, Diastolic and Mean Blood Pressure) (mmHg) |  | Hourly for the first 24 hours after mydriasis | 
| Local side effects: periorbital pallor, eyelid swelling, flushing |  | 45 minutes after the first drop instillation | 
| Adverse events including apnea, increased gastric residuals, inhibited duodenal motor activity, delayed gastric emptying, feeding intolerance, abdominal distension, vomiting, paralytic ileus, acute gastric dilatation and necrotizing enterocolitis (NEC) |  | During the 24 hours after mydriasis for ROP screening | 
| Number of participants with non-adequate mydriasis to fully visualize peripheral fundus according to the examiner |  | Upon eye examination (45 to 90 minutes after the first drop) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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microdrops, mydriasis, dilating drops, retinopathy of prematurity, ROP, screening