Can early glasses prevent the development of amblyopia in children with high refractive errors at age one?

Amblyopia (prevalence approx. 3.4%) develops in early childhood when the
child*s eyes have severe refractive error, when they squint, or both. It can
effectively be treated with glasses and patching the better eye, but treatment
should start before age 6 to be effective. Therefore, visual acuity should be
measured in all children aged 4-5 to detect amblyopia early enough. In an
effort to prevent the development of amblyopia all together, in some countries
devices are being used to measure refractive error in toddlers and, when
refractive error is severe, fit them glasses before amblyopia develops. In
Flanders, the measurement of refractive error in 1- and 2.5-year-olds began in
2012, in addition to regular vision screening with measurement of the visual
acuity at the age of 3, 4 and 5. Between 2012 and 2017 the percentage of
4-year-old glasses wearing children had risen from 4.7% to 6.4%, but it was
unknown how many cases of amblyopia had been prevented from developing. A
prospective comparison seems warranted between this new method and the current
national vision screening program in the Netherlands.

To investigate whether treating children with high refractive errors at age one
with glasses prevents the development of amblyopia.

We will perform an interventional prevention study comparing the effect of
prescribing glasses to children with high refractive error at age 1
(intervention) versus no prescription of glasses (control) on the prevalence of
amblyopia at age 4. One-year-old children will be recruited by the study
physician after visiting the children*s healthcare centres (CHCs,
*consultatiebureaus*) at 11 or 14 months. Refractive error will be determined
by retinoscopy in cycloplegia in all children. Children with refractive error
exceeding the AAPOS 2003 criteria are considered to have high refractive error
in this study. We anticipate that 8% of all children will have high refractive
error according to these criteria. These children will be randomized to the
intervention group or the control group, and will be followed up until final
visual acuity is measured at age 4. In case amblyopia or strabismus develops
during the course of the study, children will be referred for immediate
treatment, and visual acuity at the moment of referral will be used as final
measurement. In all children in the intervention group compliance with wearing
spectacles will be measured electronically. At age 4 pre-literacy skills will
be measured in the intervention group and the control group.
The majority of children, approximately 92%, will have mild or no refractive
error. After the first examination, these children will continue regular
screening at the CHCs. They will have their visual acuity measured at the age
of 4 as part of standard vision screening in the Netherlands at the CHCs. These
data will be obtained from the CHCs. If there is uncertainty about the visual
outcome at the CHC, the child will receive a supplementary evaluation. Children
with amblyopia or strabismus at the age of one will be excluded from this study
and referred for immediate treatment. Due to ethical considerations, children
with severe refractive error at the age of one, i.e. exceeding the AAPOS 2003
criteria twofold, will also be excluded from this study and referred for
immediate treatment with glasses. Due the nature and design of the study,
blinding of the researchers on site and of participants will not be possible.

Children assigned to the intervention group will be examined by the study
orthoptist one to three times yearly until final examination, and will be
fitted with glasses, based on accurate determinations of refractive error by
retinoscopy in cycloplegia. Children with high refractive error assigned to the
control group will be examined by the study orthoptist one to three times
yearly until final examination, but will not be fitted with glasses.

The expected burden and risks associated with participation can be considered
minimal. For children who have mild or no refractive error, the investigation
will be limited to the first examination at the age of 1. Children with high
refractive error are followed up 1, 2 or 3 times a year, as decided upon by the
study orthoptist, leading up to a total of additional 3-9 additional visits
until the age of 4. Each visit will take 45-60 minutes. In order to measure
refractive error accurately, retinoscopy will be done by study orthoptists
after the instillation of cycloplegic eye drops, as happens daily in clinical
practice of orthoptists and pediatric ophthalmologists. We will install 1
eyedrop of cyclopentolate 1% in each eye, which we will repeat after 10
minutes. Cyclopentolate can cause sleepiness in rare cases: children are
difficult to awaken for several minutes, but can be awoken thereafter, which is
without sequelae without exception. There are no risks associated with the
prescription of glasses at the age of one. All children will be examined at age
one by highly skilled orthoptists, who can detect amblyopia and other eye
disorders immediately and will be able to report to the parents about the
health of their children*s eyes in detail. A certain gain for both the
intervention and the control group is that the eyes of the children are
examined annually or up to three times a year by highly skilled orthoptists so
that any beginning of amblyopia or another eye disorder is timely detected.
Possible gain for participants in the intervention group includes the
prevention of amblyopia and/or a positive effect on preschool reading skills.