A visual-developmental perspective for children born very preterm

In the Netherlands, 20.000 children are born preterm each year (i.e. before 37
weeks of gestation). Over the years, their survival rates have increased due to
the intensive, high quality care that they received. As a consequence, the
number of children that sustains neurological damage has increased as well.
Because about 40% of the brain is involved in visual information processing,
there is a high chance that preterm children will develop problems in the
visual domain (e.g., visual sensory, oculomotor or visual perception problems).
Visual processing problems are known to have an adverse effect on development
in other domains, such as cognitive outcome at school age.
Despite the advanced medical diagnostic techniques that are available to detect
brain damage early in life, the detection and classification of visual
processing problems at a young age is challenging. Subtle deficits in
connectivity at a microstructural level are not detected with conventional
imaging methods. In addition, the nature and degree of structural damage is not
always related to the functional visual consequences. Moreover, before the
corrected age (CA) of 4-5 years the functional consequences, or the efficiency
of visual processing, can be challenging to assess without verbal
communication. Yet, the sooner visual rehabilitation programs can start, the
higher the chances are that they will enhance visual processing development
given the high levels of brain plasticity early in life.
Recently, a new method based on eye tracking measurements of viewing behavior
has shown promising results for assessing the efficiency of visual processing
in a nonverbal manner in children born preterm (Pel et al., 2016). It was shown
that children born preterm are at high risk of visual processing delays (VPD).
These VPD are known to be strongly correlated with brain damage-related visual
problems (cerebral visual impairment; CVI). The early and nonverbal assessments
open up the possibility to monitor or even rehabilitate VPD in these children
at a young age. Current visual rehabilitation programs are focused on
stimulating functional visual processing and viewing behavior in different
visual domains (e.g., color, motion, contrast). To date, the effectiveness of
such visual rehabilitation programs for children younger than 4 years has not
yet been investigated. Using the eye tracking-based method, the effectiveness
of rehabilitation programs in terms of the efficiency and quality of visual
processing can be examined in children born very preterm.

The main objective of this study is to investigate the effectiveness of early
visual assessment and early rehabilitation of VPD in very preterm children
(born <30 weeks GA), from 1 year CA.

Randomized controlled intervention study (RCT) integrated with standard
clinical care.
First, preterm children undergo a visual screening from 1 year CA. They are
classified as being at risk of VPD when they show abnormal viewing behavior,
i.e. delayed or incorrect gaze responses compared to age-matched controls. The
children at risk of VPD will be referred to Visio where they receive standard
care: a visual function assessment and a visual rehabilitation program.
Children are randomly allocated to a direct intervention group (starting upon
inclusion), or a control intervention group (starting 1 year after inclusion).
The control group will also receive intervention, but with a delay of one
year. During this year they will receive general developmental support and
monitoring, without specific visual components. This means that all children
will receive visual rehabilitation at an earlier age than is currently the case
(i.e. <4 years), while at the same time the reliability of an RCT is ensured.
After 1 year, the effectiveness of early visual rehabilitation will be examined
with follow-up visual and neurocognitive assessments. In addition, differences
in effectiveness of direct and postponed early visual rehabilitation are
assessed.

The intervention involves a visual rehabilitation program that is part of
standard clinical care for children at Royal Dutch Visio and that consists of
visual training and visual stimulation. The visual rehabilitation consist of a
general protocol (standardized and similar for all children) and a supplement
protocol (adapted to the specific VPD of the child). The programs will be
performed by experienced behavioral therapists in the child*s home environment
and will be done once a week, for a total duration of 9 months. Rehabilitation
will be provided to all children at risk of VPD, only the age at which it
starts differs depending on RCT allocation (i.e. upon referral at 1 year CA, or
one year later at 2 years CA).

The risks associated with participation are negligible and the burden for the
children is minimal.
Apart from the visual screening at 1 year CA, the total program is standard
care for children with (suspected) visual problems. Only the age at which this
care is applied is advanced for this study. The visual screening that all
children undergo consists of an eye tracking assessment, during which children
watch a computer screen without receiving instructions. For the children at
risk of VPD the use of eye drops during the orthoptic exam may cause a slight
burden, however, this is standard care and monitored by an ophthalmologist. The
additional visual assessments and the rehabilitation program are non-invasive
and non-restrictive, and part of standard clinical care. The study is
group-related since it involves detecting and rehabilitating VPD in a high-risk
group: children born (extremely) preterm. Benefits for all preterm children are
earlier assessments and, if applicable, earlier rehabilitation of a risk of VPD
than is the case in conventional pediatric care (i.e. from 1-2 years CA instead
of ~4 years CA).
Unanticipated results with regard to visual functioning of children in the
control group will be communicated with parents.