Background
Strabismus is a prevalent ophthalmological disorder. Cases of peripheral origin may arise from ocular trauma, myotonic dystrophy, cranial nerve syndromes, and nerve palsies—such as the reported instance of abducens nerve palsy linked to Sars-Cov-2 infection [
1,
2]. A substantial number of cases are concomitant strabismus, which are nonrestrictive and non-paralyzing, originating from possible defects in central neural pathways governing visual perception and kinesthetic control [
3,
4]. Intermittent exotropia (IXT) is a subtype of concomitant strabismus, without deficit of exotrocular muscles and nerves, and it is the most common type of strabismus in Asian children, with a prevalence of between 3.24% and 4.69% among Chinese children [
5,
6]. An increased incidence of IXT was found among preschool children in a 5-year cohort study [
6]. Intermittent exotropia can destroy the patient’s binocular vision function and has a negative impact on some psychosocial functions [
7]. Furthermore, a retrospective study found that young adults with IXT onset in childhood were found to be nearly 3 times more likely to develop neuropsychological dysfunction than the general population. Among these subjects, the incidence of attention-deficit/hyperactivity disorder (ADHD) reaches 27–31%, which is much higher than in the general public [
8,
9]. Moreover, successful strabismus correction surgery does not seem to reduce the risk of psychiatric disorders in children with IXT [
10]. Whether patients with IXT had attention deficits when they were children remains unclear. It is also unclear whether attention deficit is associated with the clinical characteristics of IXT.
Meanwhile, children with exotropia have impaired cognitive ability, including reduced working memory, weakened strategy formation functions, and poor non-verbal performance compared to normal control children [
11]. Previous studies suggested that children with exotropia (including IXT) had a different pattern of intelligence structure from the normal control children, with worse perceptual reasoning skills but better processing speeds, while no effects from clinical features were found on the intelligence of children with exotropia [
12]. As visual and auditory attention are the prerequisites of cognitive function [
13], whether attention deficit contributes to cognitive development in children with IXT remains to be explored.
The integrated visual and auditory-continuous performance test (IVA-CPT) is a commonly used test method in neuropsychology. It quantitatively measures inattention and impulsivity by allowing subjects to complete a mundane automated visual and auditory task, which is a reliable and noninvasive technique [
14]. IVA-CPT is often used clinically to diagnose disorders in which attention and control deficits lead to behavioral disorders such as ADHD and post-concussion syndrome [
15,
16]. In this study, we tested patients with IXT using IVA-CPT to explore their altered visual and auditory attention, as well as their association with clinical characteristics and cognitive development.
Discussion
In this study, we found that children with IXT had higher rates of visual and auditory attention deficits compared to their peers. The degree of strabismus, stereopsis function, and fusion control score did not significantly affect attentional abnormality, but the age of onset of strabismus did. Additionally, the study discovered a potential correlation between attention and cognitive function in these children.
Our study revealed that 44.9% of the IXT group had attentional functioning abnormalities and this ratio was about 2.6 times that of the control group. It is consistent with previous literature that patients with strabismus are more likely to suffer from psychiatric disorders in adulthood, in which abnormalities in attentional functioning mainly manifest in ADHD [
22,
23]. Previous studies also found that attention deficit occurred more in individuals with IXT: adolescents with IXT occurring in childhood receive about 2.7 times the amount of mental healthcare compared with control [
9]. The incidence of ADHD in the adolescents with uncorrected strabismus group was 1.9 times that of the control group, and those in the group with corrected strabismus were about 2.62 times more likely to have ADHD than those in the control group in Israel [
24]. Children with strabismus also had a higher risk of hyperactivity/inattention problems, with an OR of 1.64, as reported by their parents [
25]. The current study found a higher prevalence of attentional deficits compared to previous studies in children with IXT. This may be due to the fact that these studies were retrospective studies that counted the proportion of children with strabismus who had a record of being clinically diagnosed with ADHD [
10,
26], which may underestimate the real prevalence of attentional abnormalities in children with IXT. Another reason may be that the subjects with IXT in this study were children, while the subjects were adolescents or adults in previous studies. Furthermore, although the IVA-CPT we used had definite validity for attention assessment, it is not a diagnostic criterion for ADHD [
27]. After previous comparisons in different literatures we found that the level of attention in patients with strabismus differed from that of the normal population, as shown in Table
5, which is consistent with the findings of our current study. In brief, we found that children with IXT have a higher tendency for attention deficit compared with their peers.
Table 5
Characteristics of studies related to strabismus and mental disorders
McKenzie et al. (2009) | United States | Retrospective | 183; 183 | 21.9; 22.2 | 97 (53.0) | 55 (30.1) | < 0.001 | 28(15.3) | 8(4.4) | 0.001 |
Lee et al. (2022) | United States | Cross-sectional | 163,439; 11,652,553 | 8.0; 8.0 | 1416 (0.9) | 60,905 (0.5) | < 0.001 | NA | NA | NA |
Olson et al. (2012) | United States | Retrospective | 127; 127 | 20.4; 19.1 | 42 (33.1) | 20 (15.7) | 0.025 | 8 (6.3) | 6 (4.7) | 0.583 |
Mohney et al. (2008) | United States | Cross-sectional | 141; 141 | 20.3; 20.9 | 75 (53.2) | 38 (27.0) | < 0.001 | 25(17.7) | 7(5.0) | 0.001 |
Our study | China | Cross-sectional | 49; 29 | 7.8; 8.1 | NA | NA | NA | 22(44.9) | 5(17.2) | 0.013 |
A negative correlation was found between attention scores and fusional function in the current study. Children with IXT who had fusion function had lower attention levels, which we speculated may be the reason that IXT patients consume too much attention in the process of controlling eye position and fusing visual information in both eyes. We have also found evidence that children with NCS of 3 had better visual attention and visual control than those with less than 3, though this difference was not statistically significant. Overall, our results suggested that better control of the IXT may be accompanied by poorer visual and hearing attentional ability, while poorer control of IXT may result in better attentional ability. This may involve the allocation of attention resources in subjects with IXT [
28,
29]. No significant correlation was found between the level of attention and the degree of eye deviation and stereopsis function. Children with IXT were thought to have a lower health-related quality of life (HRQOL) related to the larger strabismic deviation [
30]. The HRQOL assessment also involves a number of attentional state questions (i.e., “It is hard to concentrate because of my eyes.”). Future studies would do well to explore this by extending the range of the degree of strabismus.
Our research also indicates that the level of attention is related to the onset age of IXT provided by caregivers. Specifically, attention issues are more significant when strabismus is detected at an earlier stage, and children who show signs before age four are more likely to experience attention-related issues. There was no significant correlation between the duration of IXT and attention. The random forest model showed that the predictive value of the Gini coefficient generated with age at onset was significantly higher than other indicators. Based on the above discoveries, we assumed that the age at which strabismus becomes noticeable was the most significant factor that correlated with attention development. As is widely accepted, the development of attention begins on the first day of life and is manifested by the responsive movement of the eye to external stimuli [
31]. Early attentional orienting functions are developmentally stable at one year of age, and the maintenance of attention is relatively stable at three years of age [
32]. We found that children whose IXT symptoms were evident before the age of 4 years were more likely to have accompanying attention deficits. This indicates that the onset of IXT before attention development may significantly affect children’s attention development. Our study also suggests that the earlier the onset of IXT, the more pronounced the attention deficit in children.
Children with IXT were found to have decreased attentional abilities in the study, supported by the visual pathway abnormalities present in patients with strabismus. The human attention system has two orienting networks: one located in the dorsal region, which is responsible for quick strategic eye movements, and another in the ventral area, which responds to incoming stimuli from various sources [
33]. The simultaneous transmission of the two pathways plays an important role in the bottom-up arrival of attentional signals to specific areas of the senses [
34]. Previous studies on the visual pathway and visual cortex in strabismus also supported the probability mechanism of attention deficit in individuals with IXT: those with strabismus had the volume of gray matter in the occipital lobe and parietal lobe of the brain’s visual cortex decreased, and the activation signal was lower than that of normal people, while the volume of gray matter in areas such as the prefrontal cortex increased [
35,
36]. Our finding of reduced both visual attention and auditory attention indicated that the integrated processing of visual and auditory information may also be defective in patients with IXT. Since perception of visual information enhances auditory-related frequency discrimination [
37] (e.g., loudness and auditory rhythm perception) [
38], the process of integrating vision and hearing can be influenced by binocular vision function (i.e., adults with amblyopia were found to have reduced audiovisual integration) [
39].
According to Sun et al., children with exotropia have an atypical pattern of intelligence structure, but their angle of deviation and stereoacuity do not seem to have an impact on their cognitive abilities [
12]. Our study showed that children with IXT have lower FSIQ than children of the same age, mainly in terms of reduced verbal comprehension and perceptual reasoning, and reduced processing speed. They performed poorly on the subtests of Similarities, Vocabulary, Block design and Letter-Number Sequencing. Attention is an integral part of the whole process of cognition, from the selection of information to the maintenance of its processing. We also found a correlation between the level of attention and cognitive function in children with IXT. A previous study also showed that alteration in the central brain may cause changes in the level and structure of cognition [
11], which is consistent with our findings. Defects in attention found in children with IXT may contribute to the development of cognition.
Although our study found higher rates of visual and auditory attention deficits in children with IXT compared to their peers, the visual and auditory attention levels could be associated with the age of onset of IXT. It is important to note the study’s limitations. First, the IVA-CPT test is an objective measure, but it may be affected by factors such as the time of day or the subject’s mood, potentially leading to abnormal results. At the same time, the results provided a general score on an individual’s level of attention in visual and auditory domain. Second, our sample size was relatively small, and the follow-up period was brief. Continuous monitoring of the changes in attention functions in children with IXT after surgery is necessary. Third, our findings are only a preliminary exploration of the link between IXT and reduced visual and auditory attention in childhood. It is important to assess which specific part in the cognitive process are delayed or distorted in strabismic children. Further research is needed to fully understand this connection.
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