Babies in Glasses; a Feasibility Study. (BiG)

Can Provision of Near Vision Glasses as an Early Intervention Improve Visual and Developmental Outcomes in Children With Perinatal Brain Insult? A Feasibility Study.

This is a feasibility study to begin investigating the possibility that early use of near vision glasses will improve vision in infants at risk of Cerebral Visual Impairment (CVI), leading to further improvement in other areas of development. This active intervention, starting at either 2 or 4 months of age (depending on randomisation), could be more effective than waiting until a problem is detected before giving glasses.

As this is a feasibility study, the investigators are looking at a small sample of babies (n=75) to see whether their parents/carers are willing to take part in a 3-arm study comparing two differently timed interventions to a control group, as well as looking at different aspects of the research plan in preparation for a larger final study.

Study Overview

• Status: Active, not recruiting
• Conditions: Premature Birth; Hypoxic-Ischemic Encephalopathy; Cerebral Visual Impairment; Refractive and Accommodative Disorders
• Intervention / Treatment: Device: Near vision spectacles

Detailed Description

The aim of this study is to assess the feasibility and the acceptability of randomisation and the intervention, namely near vision glasses, from parents of very young babies at risk of Cerebral Visual Impairment (CVI).

All infants are born with an immature visual system, and for vision to develop normally, a clear image needs to transmit to the visual centres of the brain.

Good vision plays an important role in facilitating normal development so if CVI goes unnoticed, it can have a damaging effect on the child's early development, and subsequent education and quality of life. Children use their sight to learn to walk, talk, think and communicate. For this reason, early intervention has the potential to have positive effects on children's vision and general development.

Previous studies have shown that up to 75% of school age children, who have CVI, have difficulty focussing their eyes on a near target, so near objects, such as their hands and parents' faces, will appear blurry. These studies also showed that wearing glasses for near focus improved vision but has not been assessed in babies.

This is a single-centre, parallel group, open-label feasibility trial to assess the feasibility of testing the effect near vision glasses (full cycloplegic refraction plus 3.00D add for near) could have on the visual and developmental outcome in babies at risk of brain injury.

Infants at risk of developing CVI include those who have had hypoxic ischaemic encephalopathy (HIE) and those born prematurely before 29 weeks gestation.

The paediatric research optometrist will enrol and assess all eligible babies of consenting families; first visit at 8 or 16 weeks corrected gestational age, depending on randomisation. Each infant will be followed up 3 months and 6-months (+/- 3 weeks) after the first visit.

There are three main areas of the assessment, which will be leading to potential primary outcome measures:

1. Visual Responses (including visual acuity and refractive status)

   At each visit, vision will be evaluated using Atkinson's battery for Child Development for Examining Functional Vision (ABCDEFV) according to the child's age and their ability. This comprises age-appropriate core vision tests (such as visual acuity and fixing and following) as well as additional tests that assess visual perception and visuomotor behaviour. If visual acuity cannot be obtained using Keeler acuity cards, as per ABCDEFV, the children will receive a measure using a Near Detection Scale (NDS).

2. General Development and Neurodevelopmental Delay

   Non-visual developmental assessments will include the Bayley Scales of Infant Development - 3rd edition (BSID-III) assessment as appropriate for age at routine neonatal clinical appointments at 3, 6,12 and 24 months (not the research clinics). A Prechtl video will also be performed at the 3-month appointment to assess the presence of fidgety movements. The presence of these movements at 3 months corrected gestational age has been strongly correlated with normal motor development.

3. Functional broadband near infrared spectroscopy (fBNIRS)

   i. Identification of changed functional haemodynamic and metabolic response to visual stimulus in infants at risk of visual dysfunction.

   ii. Assessment of changes in functional response in relation to response to glasses

   Eligible children with consenting parents will be screened for high refractive error prior to randomisation by the research optometrist to avoid post-randomisation dropouts. Evidence of high refractive error (more than -6.00D spherical equivalent or +8.00D spherical equivalent) will result in a referral to ophthalmology and exclusion from the study due to the possibility of associated ocular pathology with high refractive error.

   All of the above assessments have been organised at University College London Hospitals (UCLH). If the infant is randomised to get glasses, they will be given a near vision spectacle prescription (full cycloplegic refraction plus 3.00D add for near) to take to Great Ormond Street Hospital Eye Department dispensing optician to get the special glasses ordered.

   Expert ethical advice has been sought through the NIHR's Research Design Service to check on the dimension of potential harm (with a positive review). Each case will be monitored by the independent data monitoring and ethics committee (IDMEC) using follow up data who will report to the trial steering committee (TSC). The IDMEC, Trial Steering Committee (TSC) and Trial Management Group (TMG) will oversee the conduct of this trial.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, WC1E 6DB
    • University College London Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 month (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. All term infants undergoing therapeutic hypothermia for hypoxic ischaemic encephalopathy (HIE).
2. All preterm infants born at <29 weeks gestational age.

Specifically, all children fulfilling these criteria will be eligible. Evidence of hypo-accommodation is not required.

Exclusion criteria:

1. Infants that are still an inpatient at 8 weeks corrected gestational age.
2. Ocular exclusion criteria: children with unrelated congenital or developmental ocular abnormality such as cataract requiring surgery, genetic retinal disease, coloboma. Retinopathy of prematurity will not be an exclusion criterion.
3. Infants with high refractive error (more than -6.00D spherical equivalent or +8.00D spherical equivalent).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: A (control); First visit assessments at 8 weeks corrected gestational age. No glasses prescribed.
Experimental: B1 (intervention); First visit assessments at 8 weeks corrected gestational age. Full time spectacle wear prescribed.	Device: Near vision spectacles; Near vision spectacles prescribed for full time wear (Add+3.00DS to the full cycloplegic refraction). These glasses will be changed to reflect changes in refractive error or frame fit as appropriate at follow up.
Experimental: B2 (intervention); First visit assessments at 16 weeks corrected gestational age. Full time spectacle wear prescribed.	Device: Near vision spectacles; Near vision spectacles prescribed for full time wear (Add+3.00DS to the full cycloplegic refraction). These glasses will be changed to reflect changes in refractive error or frame fit as appropriate at follow up.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The acceptance of randomisation	This will be measured as the proportion of patients/parents who accept the offer of randomisation.	10 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Success rate in dispensing glasses to children in groups B1 and B2.	The percentage of infants dispensed vs. the total number of infants randomised to the intervention arms will be recorded at the end of the study.	6 months
Success rate of compliance with glasses for infants in groups B1 and B2.	The proportion of infants (%) who are still wearing their glasses at the 3 and 6 month follow-up appointments.	6 months
Visual Acuity	The distribution of visual acuity at the 3 and 6-month follow ups compared with visual acuity at the first visit in all 3 arms.	6 months
Retention rate	This will be measured by the median number of infants reported per month.	15 months
Refractive outcomes	The distribution of refractive outcomes (measured in dioptres) at 3 and 6-month follow ups as compared to the first visit in all 3 groups.	6 months
Evidence of impaired emmetropisation following administration of FMT	This will be measured by combining refractive error and visual acuity measures. The trial will not be feasible if there is a 2SD difference without compensatory benefit eg 2 lines improvement in visual acuity.	6 months
Determination of appropriate resource-use data collection methods	A targeted paediatric client service receipt inventory (CSRI) form has been designed specifically for this population and will be used for the duration of the feasibility study.	15 months
Accommodative outcomes	The distribution of accommodative outcomes (measured in dioptres) at 3 and 6-month follow ups as compared to the first visit in all 3 groups.	6 months
Completion of compliance questionnaires	Proportion of families completing phone questionnaire on spectacle compliance as a percentage of those in the intervention groups (B1 & B2).	6 months
Significant mechanical trauma	Significant mechanical trauma will be measured as the percentage of infants who have had an adverse event (from mechanical trauma) vs. the total number of infants prescribed glasses in groups B1 and B2. The study will not be feasible if this is more than 30% of infants in the intervention arms.	6 months
Consent rate	This will be measured as the number of infants recruited vs. number of infants, who fulfil the inclusion/exclusion criteria, approached.	10 months

Collaborators and Investigators

• Sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust
• Collaborators: University College London Hospitals; University College, London; University of Bristol; University of Ulster; National Institute for Health Research, United Kingdom; University of Reading

Publications and helpful links

General Publications

• Bullaj R, Dyet L, Mitra S, Bunce C, Clarke CS, Saunders K, Dale N, Horwood A, Williams C, St Clair Tracy H, Marlow N, Bowman R. Effectiveness of early spectacle intervention on visual outcomes in babies at risk of cerebral visual impairment: a parallel group, open-label, randomised clinical feasibility trial protocol. BMJ Open. 2022 Sep 21;12(9):e059946. doi: 10.1136/bmjopen-2021-059946.

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2021
• Primary Completion (Anticipated): June 9, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: June 24, 2021
• First Submitted That Met QC Criteria: September 7, 2021
• First Posted (Actual): September 17, 2021

Study Record Updates

• Last Update Posted (Actual): September 29, 2022
• Last Update Submitted That Met QC Criteria: September 28, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Infant; Brain Injury; Neurodevelopment; Premature Birth; Refractive Error; Baby; Glasses; Spectacle correction; CVI; Spectacles; Cerebral Visual Impairment; Visual Processing Disorder; Visual Perceptual Deficits; VPD; Accommodative Disorders; Hypo-accommodation; Accommodative lag; Hypoxic Ischaemic Encephalopathy; Near Vision Glasses; Refractive correction; Early spectacle correction; Perinatal Brain Insult; Functional broadband Near Infrared Spectroscopy; fBNIRS
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Central Nervous System Diseases; Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Signs and Symptoms, Respiratory; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Sensation Disorders; Hypoxia; Hypoxia, Brain; Brain Ischemia; Premature Birth; Brain Diseases; Hypoxia-Ischemia, Brain; Vision, Low; Vision Disorders
• Other Study ID Numbers: 18BA36

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