Comparison of the retinal thickness and retinal nerve fibre layer thickness using HD-OCT between treated and untreated children with anisometropic or strabismic amblyopia in comparison to healthy eyes.

Amblyopia is defined as the condition in which reduced visual function, caused
by reduced binocular interactions and visual deprivation during the critical
period, exists despite full optical correction and absence of observable ocular
pathology (Barrett et al. 2004; von Noorden, 2002, p246). From previous
research (Hess, 2010 and Barnes et al, 2010) we know that amblyopia causes
structural changes in the lateral geniculate nucleus (LGN) and primary visual
cortex. However, there is less certainty about whether this also affects the
retinal development regarding macular retinal thickness (MT) and peripapillary
retinal nerve fibre layer thickness (RNFLT).
In the past decade, optical coherence tomography (OCT) has been frequently used
to study the effects of amblyopia on the MT and RNFLT. Yen et al, (2004) found
a positive correlation between anisometropic amblyopia and RNFLT and
hypothesized that this is due to slowing down the normal postnatal apoptosis of
ganglion cells. Huyng et al, (2009) published the results of the Sydney
Childhood Eye Study comparing MT and RNFLT in 48 strabismic and anisometropic
amblyopic subjects and 3185 non-amblyopic subjects with use of the StratusOCT.
In contrast with the study of Yen et al, (2004) they found no significant
differences in RNFLT. However, they did find a significant larger foveal
minimum thickness in amblyopic eyes compared to the normal fellow eye and the
right eye of non-amblyopic children, respectively 5µm and 10µm (p<0.05). Also,
a second comparison was made between 33 treated and 12 untreated amblyopes.
Here the MT and RNFLT seemed to be larger in the untreated group, but due to a
small sample no significant difference was obtained. In line with this, a study
of Al-Haddad et al, (2011) revealed similar results of MT and RNFLT using
SD-OCT in amblyopic children. They compared 14 strabismic, 31 anisometropic and
20 non-amblyopic anisometropic children and found no significant differences in
the RNFLT. In contrast, the MT in anisometropic amblyopes was significantly
thicker compared to non-amblyopic anisometropic children, however this
difference was not found in the strabismic group. Wu et al, (2013) did find a
significant thicker RNFL in 72 hyperopic anisometropic amblyopes. The amblyopic
eye was compared with the fellow eye. Miki et al, (2010) studied the RNFLT
using StratusOCT in 25 patients with recovered amblyopia and 26 patients with
persistent amblyopia, to establish if differences in RNFLT are associated with
persistent amblyopia. No differentiation was made on the type of amblyopia.
There were no significant changes found in RNFLT between the two groups.
To conclude, there is increasing scope of literature on the subject, but there
are still conflicting results regarding the impairment of the MT and RNFLT in
strabismic and anisometropic amblyopic subjects. These results may be due to
small sample sizes, not using a non-amblyopic control group, use of different
instruments, and by not separating the strabismic and anisometropic amblyopes.
Furthermore, there is almost no literature available about the possible changes
in MT and RNFLT after amblyopia therapy in amblyopic children. So it is not
clear whether occlusion therapy affect the development of the retina and if
changes occur in the MT and RNFLT.
The purpose of the study is to examine the MT and RNFLT in both untreated and
treated patients with either anisometropic or strabismic amblyopia.
Furthermore, untreated and treated amblyopic patients will be compared with
non-amblyopic controls to find out if the retina of an untreated and treated
amblyopic patient show differences with that of a healthy non-amblyopic
subject. If the differences in MT and RNFLT in the amblyopic eye before and
after occlusion therapy are known, there will be a better understanding of
retinal level why visual acuity improves and a better prognosis can be given.

H1a: The macula of treated patients with anisometropic or strabismic amblyopia
is thinner than the macula of untreated patients.
H1b: The peripapillary RNFL of treated patients with anisometropic or
strabismic amblyopia is thinner than the peripapillary RNFL of untreated
patients.
H2a: The macula of untreated patients with anisometropic or strabismic
amblyopia is thicker than their fellow eye and the macula of the right eye of
healthy eyes.
H2b: The peripapillary RNFL of untreated patients with anisometropic or
strabismic amblyopia is thicker than the peripapillary RNFL of their fellow eye
and the right eye of healthy eyes.
H3a: There is no difference in macular thickness between treated patients with
anisometropic or strabismic amblyopia, their fellow eye and healthy right eyes.
H3b: There is no difference in peripapillary RNFL thickness between treated
patients with anisometropic or strabismic amblyopia, their fellow eye and
healthy right eyes.
H4a: There is no difference in macular thickness between the fellow eye of
untreated and treated patients with anisometropic or strabismic amblyopia and
healty right eyes.
H4b: There is no difference in peripapillary RNFL thickness between the fellow
eye of untreated and treated patients with anisometropic or strabismic
amblyopia and healty right eyes.

The primary objective of this study is:
- To determine the potential difference in MT and RNFLT between treated and
untreated patients with anisometropic or strabismic amblyopia.
Secondary objectives are:
- To determine the potential differences in MT and RNFLT in the untreated and
treated patient with anisometropic or stabismic amblyopia compared with normal
healthy right eyes.
- To determine the potential differences in MT and RNFLT in the fellow eye of
the treated and untreated patients with anisometropic or strabismic amblyopia.
- To determine the potential differences in MT and RNFLT in the untreated
patient with anisometropic or stabismic amblyopia and their fellow eye.
- To determine the potential differences in MT and RNFLT in the treated patient
with anisometropic or stabismic amblyopia and their fellow eye.
- To determine the the potential differences in MT and RNFLT in the fellow eyes
of the amblyopic patients and normal healthy right eyes.

Observational cross-sectional study.

Participation in the study is voluntary and has no direct benefits for the
patient. The main disadvantage regarding the OCT scan is the little extra time,
but it is also possible, but unlikely, that an unexpected abnormality in the
retina of the patient is detected. In the case that an abnormality is detected,
the parents will be directly informed and their child will be referred to an
ophthalmologist and will be withdrawn from the research.
The cyclopentolate eye drops will be used in the standard orthoptic
investigation, regardless the need for an additional OCT examination. These
drops are frequently used and the side effects are known to be minimal
(Farmaceutisch kompas, 2015). All the OCT measurements are non-invasive and not
harmful for the eyes of the child. Therefore the risks are considered
negligible and the burden for the patient is minimal.
Future patients benefit from the results, because more insight is obtained of
the development and possible structural changes in the layers of the retina
after amblyopia treatment in two types of amblyopic patients.