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Citation: Morelli, F.; Aprile, G.;
Martolini, C.; Ballante, E.; Olivier, L.;
Ercolino, E.; Perotto, E.; Signorini, S.
Visual Function and
Neuropsychological Profile in
Children with Cerebral Visual
Impairment. Children 2022,9, 921.
https://doi.org/10.3390/
children9060921
Academic Editor: Jason C. S. Yam
Received: 9 April 2022
Accepted: 16 June 2022
Published: 19 June 2022
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children
Article
Visual Function and Neuropsychological Profile in Children
with Cerebral Visual Impairment
Federica Morelli 1, 2, * , Giorgia Aprile 1, Chiara Martolini 1, Elena Ballante 3,4 , Lucrezia Olivier 1,
Elisa Ercolino 1, Eleonora Perotto 1and Sabrina Signorini 1
1Developmental Neuro-Ophthalmology Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy;
giorgia.aprile01@universitadipavia.it (G.A.); martolini.chiara@gmail.com (C.M.);
lucrezia.olivier@mondino.it (L.O.); elisa.ercolino@mondino.it (E.E.); eleonora.perotto@mondino.it (E.P.);
sabrina.signorini@mondino.it (S.S.)
2Department of Brain and Behavioural Sciences, University of Pavia, 27100 Pavia, Italy
3
BioData Science Center, IRCCS Mondino Foundation, 27100 Pavia, Italy; elena.ballante01@universitadipavia.it
4Political and Social Sciences, University of Pavia, 27100 Pavia, Italy
*Correspondence: federica.morelli02@universitadipavia.it
Abstract:
Cerebral Visual Impairment (CVI) has become the leading cause of children’s visual impair-
ment in developed countries. Since CVI may negatively affect neuropsychomotor development, an
early diagnosis and characterization become fundamental to define effective habilitation approaches.
To date, there is a lack of standardized diagnostic methods to assess CVI in children, and the role
of visual functions in children’s neuropsychological profiles has been poorly investigated. In the
present paper, we aim to describe the clinical and neuropsychological profiles and to investigate
the possible effects of visual functions on neuropsychological performance of a cohort of children
diagnosed with CVI. Fifty-one children with CVI were included in our retrospective analysis (in-
clusion criteria: verbal IQ > 70 in Wechsler scales; absence of significant ocular involvement). For
each participant, we collected data on neuropsychological assessment (i.e., cognitive, cognitive visual,
and learning abilities), basic visual functions (e.g., Best Corrected Visual Acuity—BCVA, contrast
sensitivity, and ocular motor abilities) and global development features (e.g., neurological signs and
motor development delay) based on standardized tests, according to patients’ ages. The results
showed that oculomotor dysfunction involving saccades and smooth pursuit may be a core symptom
of CVI and might have a significant impact on cognitive visual and other neuropsychological abilities.
Furthermore, visual acuity and contrast sensitivity may influence cognitive, cognitive visual, and
academic performances. Our findings suggest the importance of a comprehensive assessment of
both visual and neuropsychological functions in children when CVI is suspected, which is needed to
provide a more comprehensive functional profile and define the best habilitation strategy to sustain
functional vision.
Keywords:
cerebral visual impairment; development; visual function; neuropsychological profile;
functional vision; reading
1. Introduction
Cerebral Visual Impairment (CVI) is defined as ‘a verifiable visual dysfunction, which
cannot be attributed to disorders of the anterior visual pathways or any potentially co-
occurring ocular impairment’ [
1
]. According to this assumption, CVI derives mainly from
anatomical and/or functional anomalies of the retro-geniculate visual pathways, including
optic radiations, occipital cortex, and visual associative areas [
2
]. A dysfunction in the
oculomotor control system can also be present [
3
–
5
]. CVI has become the leading cause of
visual impairment (VI) in developed countries [
4
,
6
], partly due to better treatment strate-
gies for the peripheral causes of VI (e.g., retinopathy of prematurity, cataract, glaucoma)
and increased survival of newborns with brain injuries [
6
,
7
]. Its effects may comprise
Children 2022,9, 921. https://doi.org/10.3390/children9060921 https://www.mdpi.com/journal/children
Children 2022,9, 921 2 of 16
perceptual, oculomotor, and cognitive visual dysfunctions, occurring in isolation or con-
current [
8
–
10
]. Although traditionally associated with pathologies causing early brain
injury (e.g., periventricular leukomalacia or intraventricular hemorrhage in premature new-
borns, hypoxic-ischemic injury, Central Nervous System (CNS) infections, head trauma,
neonatal hypoglycemia) [
11
,
12
], CVI has also been reported in other disorders, such as
genetic syndromes (e.g., Williams syndrome, Turner syndrome) and neurodevelopmental
disorders (e.g., autism spectrum disorders) [
11
,
13
–
16
]. In the last few years, there has been
an improvement in the ability to diagnose CVI, with a further increase in the frequency of
its reports [6].
There is considerable consensus on the necessity to identify CVI early, since its prompt
diagnosis and characterization are fundamental to define the best treatment [
11
,
14
,
17
].
Previous works have pointed out the necessity of a classification of CVI subtypes based on
visual function [
1
,
18
,
19
]. Providing an early CVI diagnosis still seems to be difficult, espe-
cially in toddlers and in the absence of associated low vision or neuromotor disorders [
20
].
Firstly, the heterogeneity of clinical manifestations, etiologies, and associated conditions
and the lack of a multidisciplinary approach may lead to a delayed diagnosis [
11
,
14
,
21
].
Secondly, there is no international consensus on a standardized diagnostic assessment of
CVI that takes into account children’s ages and developmental abilities [
1
]; the only shared
recommendation is to adopt a multidisciplinary approach [
3
,
22
], and the different methods
for CVI evaluation are chosen depending on the context [
1
,
11
,
23
]. Given the possible
complexity of the clinical picture of CVI, a multidisciplinary and thorough assessment may
reveal the visual, developmental, and cognitive profile of a child, providing information
on how to individualize his/her habilitation [
24
]. Research in this field has proposed
descriptions of the cognitive, neuropsychological, and cognitive visual profiles in children
with periventricular leukomalacia (PVL), one of the most frequent conditions associated
with CVI [
12
,
25
,
26
], as well as screening tools such as specific questionnaires [
18
,
27
] and
assessment tools for perceptual and neuropsychological evaluation in this population [
14
].
This paper has as a first goal to describe the clinical and visual characteristics of
a cohort of children affected by CVI, along with their neuropsychological profiles. The
second aim is to evaluate whether basic visual functions (such as best corrected visual
acuity and contrast sensitivity) and ocular motor functions (fixation, smooth pursuit, and
saccades) influence the development of neuropsychological skills in children with CVI,
considering a homogeneous subgroup within the same cohort. With these purposes, we
considered neuropsychological (cognitive, cognitive visual, and learning abilities) parame-
ters, taking into account that a cognitive visual deficit may be considered part of the CVI
diagnosis. To date, few studies have been conducted to explore the relationship between
visual and cognitive functions in children with CVI [
24
,
28
,
29
]. We believe that providing
information on the effects of basic visual and ocular motor functions and development
features on neuropsychological skills in CVI might help in (a) supporting a more accurate
CVI characterization, and (b) exploring the impact of visual functions and development
features on functional vision [
30
], which is strictly connected to everyday life and academic
abilities such as reading. Furthermore, considering neuropsychological, basic visual, and
ocular motor functions and development features together would draw a more comprehen-
sive picture of CVI children’s functional profiles, allowing for the tailoring of habilitation
interventions for school and social inclusion.
2. Materials and Methods
2.1. Patients
We conducted a retrospective analysis on a cohort of pediatric patients referred to
the Developmental Neuro-ophthalmology Unit of a tertiary referral hospital for neuro-
logical conditions (IRCCS Mondino Foundation, Pavia, Italy) from 1 January 2018 to 31
December 2020. CVI diagnosis was based on the definition reported in the Introduction [
1
].
As a clinical diagnosis, it relies on observations of children’s behavior (e.g., the pattern
of peri-personal space exploration) and standardized evaluations of visual and visual
Children 2022,9, 921 3 of 16
cognitive functions, together with the support of diagnostic exams to exclude significant
ocular involvement. For the diagnostic approach, we referred to previous works on the
topic [
2
,
20
]. Medical history and diagnostic exams such as brain Magnetic Resonance
Imaging (MRI) and Visual Evoked Potentials (VEP) suggesting CNS abnormalities further
supported the diagnosis. Data concerning clinical details, neuro-ophthalmological evalua-
tions, and neuropsychological test batteries of 82 children affected by CVI from different
etiologies and aged above 4 years old (an adequate age to perform a more comprehensive
neuropsychological and visuo-cognitive evaluation) were retrospectively collected. All
the evaluations were chosen based on the ages and clinical pictures and performed for
clinical purposes by a multidisciplinary team of professionals including child neuropsychi-
atrists, ophthalmologists, psychomotor therapists, and neuropsychologists with expertise
in the field. Inclusion criteria were (1) a diagnosis of CVI; (2) a normal verbal IQ (>70) on
Wechsler scales as considered in previous studies on similar topics [25]. Exclusion criteria
were established as follows: (1) missing data for most of the clinical evaluations and tests
(17 children)
, (2) Verbal IQ < 70 on Wechsler scales (14 children), (3) presence of a peripheral
VI (i.e., caused by such conditions as retinopathy of prematurity or retinal dystrophy, which
can directly affect visual perception) (no child met this criterion). A total of 31 children
met the exclusion criteria, and 51, with a mean age of 113.07 months (range 62–213)
±
35.7,
were preliminarily included (Figure 1) for the general cohort description study. Afterwards,
a subgroup of 40 patients, homogeneous in terms of age and performed tests (mean age
121 months, range 78–187,
±
29.3) was selected to investigate possible correlations between
general clinical and visual features and neuropsychological skills. Subjects included for the
correlation analyses were all primary or middle school children, to reduce the age range
and to provide more homogeneity in cognitive tests (all children performed WISC-IV scales,
and the majority of them were tested for learning abilities).
Children 2022, 9, x FOR PEER REVIEW 4 of 18
Figure 1. Flow chart of the retrospective cohort study.
2.2. Procedure
The charts’ review focused on clinical history, neurological examination, and brain
MRI (see Tables 1 for details).
Figure 1. Flow chart of the retrospective cohort study.
Children 2022,9, 921 4 of 16
Being a retrospective analysis on data originally collected for clinical purposes, Ethics
Committee approval was not required.
2.2. Procedure
The charts’ review focused on clinical history, neurological examination, and brain
MRI (see Table 1for details).
Table 1.
General characteristics of the sample. GMFCS: Gross Motor Function Classification System.
PVL: Periventricular Leukomalacia. IVH: Intraventricular Hemorrhage. CNS: Central Nervous
System. N = 51.
Parameter Category N (%)
Sex Male 25 (49)
Female 26 (51)
Mean age (months) 113.07 (range 62–213) ±35.7
Gestational age
Term 4 (8)
Late preterm (34–36 weeks) 15 (29)
Moderate preterm (32–34 weeks) 3 (6)
Very preterm (28–32 weeks) 8 (16)
Extremely preterm (<28 weeks) 17 (33)
Unknown 4 (8)
GMFCS
Level I 14 (27)
Level II 18 (35)
Level III 15 (29)
Level IV 3 (6)
Level V 1 (2)
Neuroradiological findings **
PVL (mild/severe) 33 (65)
Sequelae of IVH or periventricular haemorrhagic Infarction 5 (10)
Combination of PVL and IVH sequelae 1 (2)
Basal ganglia/thalamus lesions (mild/moderate/severe) 1 (2)
Cortico-subcortical lesions only (watershed lesions in parasagittal
distribution/multicystic encephalomalacia) not covered under C3 1 (2)
Arterial infarctions (middle cerebral artery/other) 2 (4)
Miscellaneous 2 (4)
Normal 1 (2)
Unknown 5 (10)
Neurological Picture
Unilateral cerebral palsy 14 (27) *
Bilateral cerebral palsy 30 (59) *
Early CNS injury w/out neuromotor deficit 7 (14)
Neurologic comorbidity
(epileptic abnormalities)
Not reported 44 (86)
Reported 7 (14)
Psychiatric comorbidity
(anxiety, hyperactivity)
Not reported 43 (84)
Reported 8 (16)
Neurological signs
Diplegia 21 (41)
Hemiplegia 15 (29)
Tetraplegia 8 (16)
Motor incoordination 4 (8)
None 3 (6)
Children 2022,9, 921 5 of 16
Table 1. Cont.
Parameter Category N (%)
Motor delay
Unknown 6 (12)
Not reported 14 (27)
Reported 31 (61)
Language delay
Unknown 3 (6)
Not reported 36 (71)
Reported 12 (24)
Type of therapy
No habilitation 5 (10)
Only physical therapy 24 (52)
Physical and psychomotor 7 (15)
Physical and speech therapy 3 (7)
Physical, psychomotor, and speech therapy 2 (4)
Psychomotor only 7 (15)
Speech only 2 (4)
Psychomotor and speech 1 (2)
* All patients with cerebral palsy (CP) had a spastic form, except for one patient, who had a dyskinetic bilateral CP.
** according to Himmelmann et al. classification system [31].
When referred to our Center, all children underwent an evaluation protocol compris-
ing basic visual functions (such as visual acuity for far and near distances and contrast
sensitivity), ocular motor abilities, and neuropsychological competencies, according to
a protocol derived from the Center professionals’ experience and including cognitive
visual aspects, as in Fazzi et al. [
2
,
25
,
32
]. Basic visual functions, ocular motor abilities,
and neuropsychological assessments were performed by trained professionals (child neu-
ropsychiatrists, therapists, psychologists, and orthoptists) with expertise in the diagnosis
and habilitation of visual disorders. All the subjects also underwent an ophthalmological
evaluation performed by an ophthalmologist with neuro-ophthalmologic expertise.
Concerning visual functions, we retrospectively considered the following parameters,
according to a protocol presented by Fazzi et al. [2], categorized as exposed in Table 2:
•
Best Corrected Visual Acuity (BCVA). All children in the sample were above 4 years of
age (mean age: 113.07 months, SD:
±
35.7; age range: 62–213 months), and their visual
acuity was assessed using line tests (symbolic or literal optotypes, according to their
age), both for near (40 cm) and far (3 m) distances. Recognition acuity was measured
with the Snellen chart [33] or LEA vision test [34].
•
Contrast Sensitivity (CS): the ability to detect an image’s photometric contrast and spa-
tial frequency, evaluated with the LEA low contrast symbols test or Hiding Heidi [
35
],
based on the age and level of cooperation of the patient.
•Fixation (F), indicated as the ability to maintain fixation on a target.
•
Smooth Pursuit (SP), indicated as the ability to follow the trajectory of a slow-moving
object both on a horizontal and vertical arc.
•Saccades (SC), indicated as rapid re-fixation eye movements.
•Extrinsic Ocular Motility (OM) indicated as extraocular movements.
Table 2. Visual function (perceptual and oculomotor) characteristics of the sample.
Parameter Category N (%)
Near visual acuity
Normal (>7/10) 32 (63)
Near-normal (3–7/10) 12 (32)
Mild low vision (2–3/10) 2 (4)
Moderate low vision (1–2/10) 1 (2)
Severe low vision (0.05–1/10) 0 (0)
Partial blindness (<0.05/10) 0 (0)
Children 2022,9, 921 6 of 16
Table 2. Cont.
Parameter Category N (%)
Blindness 0 (0)
Missing data 4 (8)
Far visual acuity
Normal (>7/10) 29 (57)
Near-normal (3–7/10) 12 (33)
Mild low vision (2–3/10) 3 (6)
Moderate low vision (1–2/10) 2 (4)
Severe low vision (0.05–1/10) 0 (0)
Partial blindness (<0.05/10) 0 (0)
Blindness 0 (0)
Missing data 5 (10)
Contrast sensitivity
Normal 33 (65)
Altered 15 (29)
Missing data 3 (6)
Fixation
Normal (stable, durable, binocular) 23 (45)
Mildly altered (durable, but alternating or slight difference
between the two eyes) 21 (41)
Slightly instable and/or discontinuous 6 (12)
Instable and/or discontinuous 0 (0)
Fluctuating/eccentric 0 (0)
Occasionally erratic 0 (0)
Absent response 0 (0)
Missing data 1 (2)
Smooth Pursuit
Durable, complete, and binocular 0 (0)
Durable but incomplete/asymmetric/non binocular 6 (12)
Slightly discontinuous in all or great parts of directions 19 (37)
Clearly discontinuous/augmented latency 22 (43)
Inconstant/eccentric/fragmented 3 (6)
Only for small angle 0 (0)
Absent/no response 0 (0)
Missing information 1 (2)
Saccades
Fluid, complete, normal latency, conjugacy and precision, no
evident hypo- or hypermetria 0 (0)
Fluid but incomplete and/or asymmetric and/or not binocular
4 (8)
Slight alteration (metria, fluidity, latency) 15 (29)
Moderate alteration (metria, fluidity, latency) 27 (53)
Severe alteration/difficult to elicit (metria, fluidity, latency) 4 (8)
Absent/no response 0 (0)
Missing information 1 (2)
Extrinsic ocular motility
Normal 24 (47)
Hyperfunction/limitation 19 (37)
Paralytic limitation 6 (12)
Missing data 2 (4)
The neuropsychological assessment included (see Tables 3–5):
•Cognitive assessment, with the following tests:
The Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) [
36
] or
Wechsler Intelligence Scale for Children (WISC-IV) [
37
] were performed accord-
ing to the age of the child. For the WISC-IV scale, we collected the following
scores: (i) Verbal Comprehension Index (VCI); (ii) Perceptual Reasoning Index
(PRI); (iii) Working Memory Index (WMI); (iv) Processing Speed Index (PSI);
(v) (TIQ). For WPPSI-III scale, we collected the following scores: (i) Verbal
Comprehension Index (VCI); (ii) Performance Index (PI); (iii) Processing Speed
Index (PSI); (iv) Total Intelligence Quotient (TIQ); (v) General Language In-
Children 2022,9, 921 7 of 16
dex (GLI). Additionally, we included the weighted scores derived from each
subtest.
•Cognitive visual assessment, with the following parameters:
The Developmental Test of Visual-Motor Integration (VMI) [
38
], performed
along with its subtests, i.e., Visual Perception (VMI-V) and Motor Coordination
(VMI-M), expressed in terms of percentile scores and categorized into normal
(>16◦P), frailty (5◦–16◦P), and deficient (<5◦P);
The Developmental Test for Visual Perception (DTVP) [
39
]: General Visual-
Perceptual (DTVP-GVP), Non-Motor Visual-Perceptual (DTVP-NMVP), and
Visual-Motor Integration (DTVP-VMI) quotients werecollected and categorized
as normal (>16◦P), frail (5◦–16◦P) and deficient (<5◦P).
•
Learning abilities, with the following parameters, categorized as normal or deficient
based on the Z-score:
The Battery for Dyslexia and Developmental Dysorthography (DDE-2) [
40
],
which is a commonly used Italian battery for the assessment of dyslexia and
dysorthography. Specifically, the battery evaluates the ability to read and write
both meaningful (DDE-MF) and non-meaningful (DDE-NMF) words by taking
into account speed (VEL) and accuracy (ERR);
The MT-3 test [
41
], which is a currently used Italian instrument aimed to evaluate
comprehension (MT-COMP), reading accuracy (MT-RCOR), and reading speed
(MT-RVEL) by proposing tests appropriate to the patient’s level of education.
Table 3.
Cognitive assessment. N indicates the number of subjects who performed the test or had
an interpretable result, with the percentage of subjects that completed the test according to age (see
Materials and Methods section for abbreviations).
Cognitive Assessment N (%)
WPPSI-III
VCI 9 (90)
PI 9 (90)
PSI 4 (40)
TIQ 8 (80)
GLI 3 (30)
WISC-IV
VCI 36 (87)
PRI 32 (78)
WMI 37 (90)
PSI 35 (85)
TIQ 29 (71)
Table 4.
Cognitive visual assessment. N indicates the number of subjects who performed the test or
had interpretable results.
Visuo-Cognitive Assessment Category N
VMI 1
VMI a
normal (>16◦p) 18
frailty (5◦–16◦p) 4
deficit (<5◦p) 20
total 42
VMI-V b
normal (>16◦p) 20
frailty (5◦–16◦p) 10
deficit (<5◦p) 11
total 41
Children 2022,9, 921 8 of 16
Table 4. Cont.
Visuo-Cognitive Assessment Category N
VMI-M c
normal (>16◦p) 10
frailty (5◦–16◦p) 9
deficit (<5◦p) 21
total 40
DTVP 2
DTVP-GVP a
normal (>16◦p) 14
frailty (5–16◦p) 6
deficit (<5◦p) 14
total 34
DTVP-NMVP b
normal (>16◦p) 15
frailty (5◦–16◦p) 14
deficit (<5◦p) 12
total 41
DTVP-VMI c
normal (>16◦p) 8
frailty (5◦–16◦p) 13
deficit (<5◦p) 13
total 34
1
. Developmental Test of Visual-Motor Integration: (
a
) VMI (global score); (
b
) VMI-V (Visual Perception);
(
c
) VMI-M (Motor Coordination)
2
. Developmental Test for Visual Perception: (
a
) DTPV-GVP (Developmental
Test for Visual Perception—General Visual-Perceptual); (
b
) DTPV-NMVP (Non-Motor Visual-Perceptual); (
c
)
DTPV-VMI (Visual-Motor Integration).
Table 5.
Learning abilities assessment. N indicates the number of subjects who performed the test or
had interpretable results.
Leaning Abilities Assessment Category N
DDE-2 1
MF a
VEL
normal 18
deficit 14
total 32
ERR
normal 26
deficit 5
total 31
NMF b
VEL
normal 12
deficit 14
total 26
ERR
normal 22
deficit 6
total 28
MT-3 2
COMP a
normal 22
deficit 13
total 35
RCOR b
normal 21
deficit 5
total 26
Children 2022,9, 921 9 of 16
Table 5. Cont.
Leaning Abilities Assessment Category N
RVEL c
normal 16
deficit 12
total 28
1
. Battery for Dyslexia and Developmental Dysorthography: (
a
) Meaningful words—Velocity and Error;
(
b
) Non Meaningful words—Velocity and Error.
2
. MT Test: (
a
) Reading comprehension; (
b
) Reading correctness;
(c) Reading velocity.
2.3. Data Analysis and Statistics
Data were analyzed by using the free software R Version 4.1.2 (Free Software Founda-
tion, Boston, MA, USA). To evaluate whether our sample had sufficient power to compute
a statistical analysis on each dependent variable (i.e., cognitive, cognitive visual, learn-
ing), we computed the power analysis by calculating the sample size on the free software
G*Power 3.1 (Faul et al., 2009 [
42
]), based on the following parameters (see Sakki et al.,
2021 [19]):
−Effect size dz: 1.20;
−αerr. prob. = 0.05;
−Power (1-βerr. prob.) = 0.95.
The calculated sample size was = 10. Consequently, we excluded neuropsychological
variables with a total sample smaller than 10 subjects (see Tables 3–5in the main text for
further details), i.e., The Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III).
In our sample, the variable with the higher number of missing values had 29 observations.
The numerical variables (related to cognitive assessment) do not present deviation
from the normal distribution (pvalues of the Shapiro-Wilk test > 0.1 and visual inspection
of qqplots; histograms are shown in the Figure S1 in the
Supplementary Materials
), so
parametric models are adopted. We ran linear models separately on each part of cognitive
assessment (WISC-VCI, WISC-PRI, WISC-WMI, WISC-PSI, WISC-IQ), considered as de-
pendent variables. Each model considers the set of visual functions as covariates (BCVA,
visual acuity for near distance, fixation, pursuit, saccades, ocular motility, contrast sensitiv-
ity). We ran ordinal regressions to investigate the influence of the same set of covariates
on visuo-cognitive parameters (VMI, VMI-V, VMI-M, DTVP-GVP, DTVP- NMVP, DTVP-
VMI, which represent target variables for each model). Finally, we ran logistic regressions
to investigate the influence of the same covariates on learning abilities (DDE-MF-VEL,
DDE-MF-ERR, Dysorthography, DDE-NMF-VEL, DDE-NMF-ERR, MT-RVEL, MT-RCOR,
MT-COMP, which represent target variables for each model).
3. Results
In the present work, we evaluated the most relevant effects of basic visual functions,
ocular motor abilities, and global development features on neuropsychological (including
cognitive visual) performances. Results concerning the descriptive data for the cohort are
reported in Tables 1and 2. Concerning statistical analyses, we report the significant results
obtained. Other results are exposed in Supplementary Materials (Tables S1 and S2).
Concerning basic visual functions, BCVA for distance was shown to be negatively
correlated with the WISC-IV scale’s Perceptual Reasoning Index (PRI, pvalue = 0.001) and
Processing Speed Index (PSI, pvalue = 0.007), with worse performances in children with
worse visual acuity. The same trend was found for the Developmental Test of Visual-Motor
Integration in its global (VMI, pvalue = 0.03) and Visual Perception (VMI-V;
pvalue = 0.006
)
scores. On the contrary, BCVA for near showed an opposite influence on VMI and VMI-V
(pvalue = 0.03 for both), with worse performances in children with better visual acuity.
An altered Contrast Sensitivity was found to negatively influence the WISC-IV scale’s
Working Memory Index (WMI, pvalue = 0.01), along with the Total Intelligence Quotient
(TIQ, pvalue = 0.04). Another interesting result concerning the impact of contrast sensitivity
was obtained from applying linear regression analysis to learning abilities: an altered
Children 2022,9, 921 10 of 16
contrast sensitivity showed a negative impact on a subtest concerning text comprehension
(MT-text Comprehension—MT-COMP, pvalue = 0.007), and a borderline significance
was also found regarding the DDE-2 Meaningful Words reading speed (DDE-MF-VEL,
pvalue = 0.08).
Concerning ocular motor abilities, a more qualitatively durable and/or complete
Smooth Pursuit was found to positively influence the WISC-IV scale’s Processing Speed
Index (pvalue = 0.02) and all the VMI subscores (VMI pvalue = 0.04; VMI-V pvalue = 0.01;
VMI-M pvalue = 0.03).
Furthermore, the Visual-Motor Integration subtest of the Developmental Test for Visual
Perception (DTVP-VMI) was found to be positively influenced by a qualitatively better
Extrinsic Ocular Motility (pvalue = 0.02), and better organized Saccades (pvalue = 0.04).
For further details on the statistical analyses results, see Tables S1 and S2 in
Supplementary
Materials.
4. Discussion
In the present paper, we describe the clinical, visual, and neuropsychological profile
of a cohort of 51 children diagnosed with CVI. Furthermore, we investigate the possible
influence of basic visual functions (e.g., Best Corrected Visual Acuity—BCVA, contrast
sensitivity—CS) and ocular motor abilities (fixation, smooth pursuit, saccades, and extrinsic
ocular motility) on the neuropsychological profile (i.e., cognitive, cognitive visual, and
learning abilities) in a subgroup of children from the same cohort. Our aims are in line with
the current literature on habilitation [
43
] in children, which encourages an approach based
on the individual’s functional profile. In this view, an early and comprehensive evaluation
approach to every child with diagnosed or suspected CVI would be helpful to tailor their
habilitation program.
4.1. Clinical, Visual Function and Neuropsychological Profiles
Most of the subjects in our cohort (43/51, 84%) were born prematurely and 86% were
diagnosed with Cerebral Palsy (CP). Moreover, the majority of them showed Periventricular
Leukomalacia (PVL), sequelae of Intraventricular Hemorrhage (IVH) or periventricular
hemorrhagic infarction in brain MRI (see Table 1for further details), findings frequently
associated with premature birth [
31
,
44
]. These data are in accordance with the current
literature on CVI causes and associated conditions. Perinatal problems due to premature
birth are considered the most common reason for acquired CVI [
45
,
46
], and prematurity is
frequently also reported in cases of CVI with multiple etiologies [
47
]. Even though an etio-
logical and radiological analysis goes beyond the purpose of this paper, these results may
have interesting implications for the clinical management and follow-up of these children.
Indeed, ‘at risk’ children who are already under clinical follow-up would benefit from early
CVI screening, requiring attention to medical history and clinical characteristics such as
VI in absence of an ocular problem of such entity to justify a functional deficit
[1,4,10,17]
.
Children above 3 years of age would also benefit from screening tools such as specific
questionnaires [10,18].
Concerning visual function profiles, CS and BCVA evaluated for far and near distance
in our sample and were mainly within the normal or near-normal range. A slightly bigger
percentage of children in the ‘mild low vision’ group was found for near distance, which
could be interpreted on the basis of a foveal crowding phenomenon impairing symbol
recognition in linear optotypes [
48
]. Although low vision and altered CS are common signs
of CVI [
2
,
49
], good values of BCVA in CVI have also been reported [
50
,
51
]. Furthermore,
some authors have described an improvement of BCVA during infancy in the absence
of ophthalmologic or neurologic comorbidities (e.g., epilepsy) [
47
,
52
]. These could be
possible explanations for the presence of normal or near-normal BCVA values in our
sample, in which the mean age at evaluation was 9 years old and no child suffered from
significant neurologic comorbidities such as epilepsy. Nonetheless, our findings should be
interpreted with caution because of the retrospective nature of this paper and the restrictive
Children 2022,9, 921 11 of 16
inclusion criteria. In fact, only children with sufficient BCVA to perform neuropsychological
assessment were included. On the other hand, it is worth highlighting that clinically tested
visual abilities might not represent visual functioning in everyday life [
22
,
53
]. Indeed, as
explained in a valuable work by Colenbrander [
30
], visual function performances (e.g.,
‘how the eye functions’) should not be considered without an appropriate functional visual
behavior assessment (e.g., ‘how the person functions’), which should consider factors such as
the subject’s environmental and social context. Many authors state that the most frequent
symptoms observed in children with normal VA are visual perception and integration
dysfunctions, due to damage to the associative areas (dorsal and ventral streams) [
54
], and
ocular motor abnormalities [
2
,
55
]. Accordingly, visual function profiles in our cohort were
dominated by abnormalities in ocular motor functions (i.e., smooth pursuit and saccades).
An impairment of such functions in patients with CVI has been widely investigated [
8
,
56
,
57
]
and may reflect dysfunctions in the oculomotor system and/or in the dorsal stream pathway
involved in ocular movements and visually guided actions [
5
,
8
,
56
,
58
–
60
]. Nevertheless,
most previous studies have characterized oculomotor dysfunction in children with CVI,
mainly focusing on the presence of strabismus and/or nystagmus [
26
,
32
,
61
] or on the
description of possible visual disorders in CP [
2
,
5
]. To our knowledge, only a few clinical
and qualitative characterizations of these features have been performed [
2
,
5
]. Among
quantitative studies, Newsham et al. [
62
] examined saccades and smooth pursuit in a group
of very preterm children without major CNS involvement, revealing a modest latency in
pursuit, while Jacobson et al. [
63
] reported altered smooth pursuit in children with PVL.
An interesting prospective study by Kaul et al. [
64
] found significant correlations between
‘gaze gain’ (i.e., a combination of visual tracking through smooth pursuit, head movements,
and saccades), quantitatively evaluated with electro-oculography at the age of 4 months,
and later cognitive, language, and fine motor development, evaluated with the Bayley
Scales for Infant Development at 3 years of age.
Concerning neuropsychological aspects, the total IQ mean value was in the borderline
range (we specify that a normal verbal IQ was an inclusion criterion). The majority
of children who performed the relative tests showed impairments in cognitive visual
performances, manifesting themselves as frailties or as frank deficits, and several children
had difficulties in object recognition tasks; these results confirm the notion that cognitive
visual deficits may be a core symptom of CVI [
11
,
21
]. Even in a relatively small sample, our
results seem to confirm the ones in a recent work from Ben Itzhak et al. [
18
,
24
] concluding
that deficits in ‘ventral’ tasks such as object recognition might be a specific characteristic
in children with CVI [
24
]. Concerning reading abilities evaluated with tests standardized
for the Italian population, our sample showed an involvement of reading speed, with
minor compromise of comprehension and accuracy. Such a finding could be related to
visual characteristics, such as oculomotor impairment and the crowding effect, but also to
attention, a function that is frequently altered in premature children [65,66].
4.2. Relation between Visual Functions and Neuropsychological Profile
In the second part of our work, we aimed to evaluate whether basic visual functions
and ocular motor abilities would impact on neuropsychological performances in a group
of 40 children with CVI.
Concerning basic visual functions, we found that children with normal BCVA values
(>7/10) performed significantly better both in the Perceptual Reasoning Index (PRI) and in
the Processing Speed (PSI) of the Wechsler intelligence scales. In addition, the Develop-
mental Test of Visual-Motor Integration (VMI), in its global and visual perceptual (VMI-V)
performances, appeared to be influenced by visual acuity for far distance (p= 0.03 and
p= 0.006
, respectively). This finding would suggest that an optimal level of visual experi-
ence is important for perceptual and abstract visual tasks, especially when characterized
by high visual involvement and requiring visual–motor coordination. On the contrary,
higher levels of visual acuity for near distance seem to negatively influence both global VMI
and VMI-V performances. Such an unexpected result could be explained with the sample
Children 2022,9, 921 12 of 16
characteristics (the near-distance visual acuity was in the normal or near-normal range
for 33/40 subjects, and only 3 subjects presented moderate low vision), in which severely
visually impaired children were not present. In addition, from a theoretical perspective, we
know that visual acuity alone is not sufficient to explain the performance in visuo-cognitive
tasks requiring visuo-spatial abilities, which are influenced by the involvement of non
primary-perceptive cerebral areas such as the dorsal stream [2,55].
The influence of BCVA on cognitive and visuo-cognitive tasks would argue in favor
of a multidisciplinary approach, both in the evaluation and in the re-habilitation settings,
in children with CVI. On one hand, visual acuity evaluation should always be considered
when interpreting a child’s cognitive performance, especially when the cognitive profile is
uneven with worse performances in processing speed, perceptual reasoning, and visual–
motor coordination. On the other hand, sustaining visual acuity from an early age (for
example, with multisensory activities) might be important to promote the integration of
vision, implement perceptual development [
67
], and finally reduce the frailties that may
already exist in such tasks due to the involvement of associative areas [2,55].
Another interesting finding concerning basic visual functions is the influence of con-
trast sensitivity (CS) on reading tasks. Specifically, CS seems to influence text comprehen-
sion tasks with a strong level of significance (p= 0.007) and word reading speed, though
without reaching statistical significance (p= 0.08). Such a finding may have significant
implications in light of the above-mentioned importance of environmental adaptations
to sustain both visual function and functional vision in children [
30
,
43
]. Indeed, adapt-
ing school environment and material, for example, providing adequate illumination and
high-contrast sheets, would sustain and improve the child’s reading performance.
Concerning ocular motor abilities, we found a significant influence on the same neu-
ropsychological tasks requiring good visual–motor and visual perceptive abilities described
for basic visual functions. In fact, a discontinuous smooth pursuit and altered saccades
seem to affect all the components (visual and motor) of the Visual Motor Integration tasks.
These results are in line with the hypothesis of Kaul et al., who postulated that higher visual
functions (evaluated, for example, with visual motor integration and perceptual reasoning
tasks) may be influenced by oculomotor abilities in premature children [
64
], and would
argue in favor of early oculomotor training to sustain systematic visual exploration.
To our knowledge, this is one of the first works investigating a role of CVI in school
performances. Literature suggests that deficits in functions such as attention, ocular motil-
ity, and visuospatial processing (which are frequently associated with CVI) may have a
repercussion on academic performance, which is considered an aspect of functional vi-
sion [
30
,
68
,
69
]. In our study we found promising results regarding the influence of contrast
sensitivity on reading abilities. No significant influence of oculomotor abilities on reading
emerged from our analyses, probably due to the sample size and homogeneity. Never-
theless, reading abilities appear to be related to all the components of vision (perceptual,
oculomotor, and cognitive) and may benefit from a comprehensive rehabilitation of these
aspects from an early age [
70
,
71
]. We believe further studies on this topic are necessary,
considering bigger samples of patients, attending different school grades and using ho-
mogeneous evaluation tools, to better define the learning profiles of children with CVI
and reveal whether they could benefit from specific adaptations or training programs,
also based on visual functioning. Visual functions and neuropsychological assessments
considered in our analyses were performed allowing self-adopted compensation strategies
(e.g., head turn, visuo-tactile guidance) and providing appropriate and personalized envi-
ronmental adaptations depending on specific visual characteristics (e.g., bookrest, room
illumination, adequate letters size and line-spacing when testing learning skills). A focus
on such environmental adaptations would be recommended in home and school settings
and, in general, in the child’s everyday environments. We believe such an approach, in line
with current literature [
43
], would provide more insights on children’s functional vision,
being worthy of consideration when planning tailored strategies in a multidimensional
habilitation approach [70,72] for children with CVI.
Children 2022,9, 921 13 of 16
Some limitations emerged from the present study. Firstly, its retrospective nature led
to some missing data and a reduced homogeneity of evaluations (especially concerning
learning abilities), since they were applied for clinical purpose and were necessarily limited
by children’s ages and clinical pictures. For example, data on visual field examination could
also have proved useful for the analyses and interpretation of results, but a standardized
evaluation was unavailable due to the ages and lack of cooperation of the children. Secondly,
the inclusion criteria (particularly a verbal IQ > 70) reduced the number of the sample
and the width of the spectrum of manifestations, excluding children with a more severe
clinical picture and limiting the number of variables to consider. Further research studies
are needed that guarantee greater heterogeneity of age and clinical pictures and more
homogeneous assessments.
5. Conclusions
Our study showed that the visual function profile may contribute to better defining the
neuropsychological characteristics of a child with CVI and highlighted the importance of
evaluating visual characteristics to defining a functional profile for guiding the habilitation
process of children affected by Cerebral Visual Impairment [73].
Among CVI symptoms, particular attention should be given to oculomotor dysfunc-
tions as a cardinal feature of this condition since an early age. Furthermore, a deficit in
such visual functions as visual acuity, contrast sensitivity, smooth pursuit, and saccades
may negatively affect the development of cognitive visual functions and learning abili-
ties (especially reading skills). Since it has been reported that CVI can negatively affect
children’s learning [
3
], we believe that further studies on this topic might help to shed a
light on the possible effects of visual function deficits on reading and computing skills.
Finally, our findings showed the necessity of a constant monitoring and the definition of an
effective habilitation strategy for visual functions (i.e., perceptual and oculomotor abilities)
to sustain the development of functional vision and provide children with higher levels of
autonomy and inclusion.
Supplementary Materials:
The following supporting information can be downloaded at: https:
//www.mdpi.com/article/10.3390/children9060921/s1, Figure S1: Histograms representing the
distribution of numerical variables for cognitive tests and the relative p values obtained with Shapiro–
Wilk tests. WISC: Wechsler Intelligence Scale for Children. IQ: Intelligence Quotient. VCI: Verbal
Comprehension Index. PRI: Perceptual Reasoning Index. WMI: Working Memory Index. PSI:
Processing Speed Index; Table S1: Linear regression models for cognitive assessment; Table S2:
Ordinal and logistic regression models for cognitive visual and learning abilities as-sessment.
Author Contributions:
F.M., G.A. and S.S. contributed to study conception, design, and manuscript
writing. E.E., L.O. and E.P. were directly involved in the evaluations, and contributed to data collection
and manuscript writing. C.M. and E.B. performed data analyses and contributed to manuscript
writing and revisions. All authors have read and agreed to the published version of the manuscript.
Funding: This work was supported by grants of the Italian Ministry of Health to 2020.
Institutional Review Board Statement:
The work was conducted in accordance with the Declaration
of Helsinki. Being a retrospective analysis on data originally collected for clinical purposes, approval
from the Institutional Review Board was not required.
Informed Consent Statement:
Ethical review and approval was not required in accordance with
the local legislation and institutional requirements. Written informed consent to be part of this
retrospective research was provided by the participants’ legal guardians/next of kin according to the
guidelines of the Declaration of Helsinki.
Data Availability Statement:
Data supporting reported results can be found at the link 10.5281/
zenodo.5336819 (9 March 2022).
Acknowledgments:
Special thanks go to all the children and families for their willing participation
in our clinical and research activity. We also wish to thank all the professionals who share everyday
life with us and the Mariani Foundation for its ongoing support.
Children 2022,9, 921 14 of 16
Conflicts of Interest:
The authors declare that the research was conducted in the absence of any
commercial or financial relationships that could be construed as a potential conflict of interest.
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