Pharmacokinetics and Safety of Dexamethasone Eye Drops in Preterm Infants

Pharmacokinetics and Safety of Dexamethasone Eye Drops in Preterm Infants With Retinopathy of Prematurity- a Feasibility Study

Background and study aims

When an infant is born premature, the blood vessels in the eyes have not developed fully on the retina, and can start to grow incorrectly and result in blindness. To prevent this from happening, premature infants are often screened, and treated with laser or injections into the eye to prevent retinal detachment. A new treatment strategy with steroid eye drops have been found to prevent serious blood vessel growth. The treatment is commonly used in older children and adults to treat different inflammatory conditions, but how the drop is absorbed in premature infants and if there is any risk of side-effects is poorly investigated. The aim of this study is to document how the steroid drop is absorbed and excreted in premature infants and to study if there is a risk of any side effects.

Who can participate?

Premature infants born before gestational age week 30, that undergo eye-screening at Sahlgrenska University Hospital in Gothenburg and Skånes University Hospital in Malmö and Lund or at Helsingborg Hospital, in the need for steroid eye-drop treatment against pathological vessels. It is not possible to participate if the infant has received systemic steroid treatment 2 weeks prior to the eye-drop treatment, or has an ongoing ocular infection.

What does the study involve?

The study involves blood and saliva samples according to a specific protocol designed to be able to learn about the uptake and breakdown of the steroid in premature infants. Measurements of blood pressure, growth and a few urine samples will also be collected during the treatment period usually lasting for some weeks.

At 2.5 and 5 years of age, visual acuity, refractive errors and retinal thickness measurements will be noted.

What are the possible benefits and risks of participating?

The infant will receive steroid eye-drops that have been noted to heavily reduce the number of infants that develop retinal changes that require injections or laser treatment.

The blood samples have been reduced to an absolute minimum in volume and numbers, but will entail some extra samplings from the infant.

The infant will be rigorously checked with regard to any possible side effects from the steroid treatment. Possible but unlikely side effects from the low dose in eye drops are; elevated blood pressure, retarded growth, lowered endogenous steroid production during the eye-drop treatment, increase in blood glucose, and an increase in intra-ocular pressure.

Study Overview

• Status: Completed
• Conditions: Retinopathy of Prematurity
• Intervention / Treatment: Drug: Dexamethasone Ophthalmic

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Skåne County
    • Lund, Skåne County, Sweden, 22185
      • Skane University Hospital
  • Västra Götaland County
    • Gothenburg, Västra Götaland County, Sweden, 41685
      • Sahlgrenska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 2 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Infants screened for retinopathy of prematurity (ROP) at Sahlgrenska University Hospital in Gothenburg, at Skåne University Hospital in Malmö and Lund and at Helsingborg Hospital.
• zone I stage 1 or 2 ROP without plus disease, posterior zone II stage 2 ROP without plus disease, or zone II stage 3 ROP without plus disease. ROP needs to be documented by digital widefield photography and classification confirmed by two ophthalmologist.

Exclusion Criteria:

• ocular infection
• systemic steroid treatment within two weeks before the start of drop treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Dexamethasone treated infants; 15 infants that receive dexamethasone eye drops for treatment of retinopathy of prematurity will be included, and both serum and saliva samples will be collected in order to find out the pharmacokinetic properties of dexamethasone in eye drops according to a pre-specified sampling scheme specifically designed for this purpose by experts in pediatric pharmacokinetics.

Drug: Dexamethasone Ophthalmic; one drop daily in each eye with retinopathy of prematurity of a predefined stage.; Other Names: dexafree

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics: half-life of plasma concentrations of dexamethasone during treatment with dexamethasone eye drops measured with mass spectrometry.	Half-life of dexamethasone- t½, hours	up to 14 weeks
Pharmacokinetics: maximum plasma concentration of dexamethasone during treatment with dexamethasone eye drops measured with mass spectrometry.	Maximum plasma concentration- Cmax, nmol/L	up to 14 weeks
Pharmacokinetics: saliva koncentrations of dexamethasone during treatment with dexamethasone eye drops.	Half-life of dexamethasone- t½, hours	up to 14 weeks
Pharmacokinetics: saliva koncentrations of dexamethasone during treatment with dexamethasone eye drops measured with mass spectrometry.	Maximum saliva concentration- Cmax, nmol/L	up to 14 weeks
Pharmacokinetics: time to reach maximum plasma concentration of dexamethasone during treatment with dexamethasone eye drops measured with mass spectrometry.	tmax, hours	up to 14 weeks
Pharmacokinetics: time to reach maximum saliva concentrations of dexamethasone during treatment with dexamethasone eye drops measured with mass spectrometry.	tmax, hours	up to 14 weeks
Pharmacokinetics: area under the concentration-time curve for plasma dexamethasone from time point 0 to time t of the last measured concentration above the limit of quantification time.	AUC0-t, nmol.h/L	up to 14 weeks
Pharmacokinetics: area under the concentration-time curve for saliva dexamethasone from time point 0 to time t of the last measured concentration above the limit of quantification time.	AUC0-t, nmol.h/L	up to 14 weeks
Pharmacokinetics: area under the concentration-time curve for plasma dexamethasone from time point 0 to infinity;	AUC0-∞, nmol.h/L	up to 14 weeks
Pharmacokinetics: area under the concentration-time curve for saliva dexamethasone from time point 0 to infinity;	AUC0-∞, nmol.h/L	up to 14 weeks
Pharmacokinetics: apparent total body clearance	CL/F, L/h	up to 14 weeks
Pharmacokinetics: apparent volume of distribution	Vz/F, L	up to 14 weeks
Safety: serum concentrations of endogenous corticosteroids before, during and after treatment with dexamethasone eye drops measured with mass spectrometry.	Endogenous levels of corticosteroids, nmol/L	up to 14 weeks
Safety: saliva concentrations of endogenous corticosteroids before, during and after treatment with dexamethasone eye drops.	Endogenous levels of corticosteroids, nmol/L	up to 14 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To describe if dexamethasone eye drops delay the intervention for type 1 ROP in cases without regression by calculating the time from detection of type 2 ROP to type 1 ROP	Time from detection of type 2 ROP to type 1 ROP, days	Up to 14 weeks
To describe if dexamethasone eye drop treatment before intervention for type 1 ROP reduces the number of recurrences after the intervention.	recurrences after laser/anti-VEGF treatment, percentage	Up to 14 weeks
To find out if retinal morphology measured with optical coherence tomography is affected by dexamethasone eye drops at 2.5 years of age.	Retinal thickness, micrometers	after 2.5 years
To find out if retinal morphology measured with optical coherence tomography is affected by dexamethasone eye drops at 5 years of age.	Retinal thickness, micrometers	after 5 years
To find out if dexamethasone eye drops affect visual acuity at 2.5 years of age	Visual acuity according to Snellen, fraction	after 2.5 years
To find out if dexamethasone eye drops affect refractive errors at 2.5 years of age	Refractive power, diopters	after 2.5 years
To find out if dexamethasone eye drops affect visual acuity at 5 years of age	Visual acuity according to Snellen, fraction	after 5 years
To find out if dexamethasone eye drops affect refractive errors at 5 years of age	refractive power, diopters	after 5 years

Collaborators and Investigators

• Sponsor: Region Skane
• Investigators: Principal Investigator: Hanna Maria Öhnell, PhD, Ophthalmology, dep. of clinical sciences Lund, Lund University, Skåne University Hospital, Sweden; Principal Investigator: Ann Hellström, prof, Ophthalmology, inst. of neuroscience and physiology, University of Gothenburg, Sweden

Publications and helpful links

General Publications

• Ohnell HM, Andreasson S, Granse L. Dexamethasone Eye Drops for the Treatment of Retinopathy of Prematurity. Ophthalmol Retina. 2022 Feb;6(2):181-182. doi: 10.1016/j.oret.2021.09.002. Epub 2021 Sep 10. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2022
• Primary Completion (Actual): March 4, 2026
• Study Completion (Actual): March 4, 2026

Study Registration Dates

• First Submitted: May 13, 2022
• First Submitted That Met QC Criteria: May 19, 2022
• First Posted (Actual): May 24, 2022

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: pharmacokinetics; retinopathy of prematurity; dexamethasone
• Additional Relevant MeSH Terms: Infant, Premature, Diseases; Infant, Newborn, Diseases; Eye Diseases; Retinal Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Retinopathy of Prematurity; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: 2022-00536-01; 2020-004933-19 (EudraCT Number)

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
• product manufactured in and exported from the U.S.: No