Intermittent exotropia increasing with near fixation: a "soft" sign of neurological disease

¹ Department of Ophthalmology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
² Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA

Correspondence to:
Paul H Phillips
MD, Arkansas Children’s Hospital, 800 Marshall Street, Little Rock, AR 72202, USA; phillipspaulh{at}uams.edu

Accepted for publication 1 March 2005

ABSTRACT
Aim: To examine the association of distance-near disparity with neurological disease in children with intermittent exotropia.

Methods: A retrospective analysis was performed of the medical records of all children with intermittent exotropia examined at the Arkansas Children’s Hospital between 1989 and 2002. The study group consisted of children with intermittent exotropia who had a near deviation that exceeded the deviation at distance by at least 10 prism dioptres. The control group consisted of children with intermittent exotropia who had a distance deviation greater than or equal to the deviation at near. The main outcome measures were the prevalence of neurological abnormalities in the study and control groups.

Results: Among the 29 patients in the study group, 19 (66%) had a history of concurrent neurological abnormalities. Associated neurological conditions included developmental delay (10 patients), attention deficit disorder (four patients), cerebral palsy (four patients), history of intracranial haemorrhage (four patients), periventricular leucomalacia (three patients), seizures (two patients), cortical visual impairment (two patients), hydrocephalus (one patient), history of anoxic brain damage (one patient), history of encephalitis (one patient), and autism (one patient). Among the 37 patients in the control group, seven (19%) had a history of concurrent neurological abnormalities. The difference in the prevalence of neurological disease between the study group and the control group was significant (p = 0.0002).

Conclusion: Intermittent exotropia increasing with near fixation is associated with neurological disease in children.

Keywords: exotropia; neurological disease; near fixation

REPRINTED FROM SEPTEMBER ISSUE
Children with intermittent exotropia often have an exodeviation that increases with distance fixation.^1,2 However, some children exhibit an exodeviation that increases during near fixation. It has been our impression that the latter group frequently has associated neurological or neurodevelopmental disorders. To test this hypothesis, we retrospectively reviewed the medical records of our patients with intermittent exotropia.

METHODS
Retrospective analysis of the medical records of all children with intermittent exotropia examined at the Arkansas Children’s Hospital between 1989 and 2002. The study group consisted of children with intermittent exotropia whose near deviation was at least 10 prism dioptres greater than their distance deviation. The control group consisted of children with intermittent exotropia who had a distance deviation greater than or equal to the deviation at near. Children who had strabismus surgery were categorised by ocular motility measurements obtained before their strabismus surgery. Children who had undergone strabismus surgery before examination by one of the investigators were excluded from the analysis. In addition, children who had a near deviation that was less than 10 prism dioptres greater than the distance deviation, who had an inconsistent distance/near disparity, or who were uncooperative for distance and near measurements were excluded from the analysis. None of the patients had amblyopia, ptosis, anisocoria, nystagmus, limited ductions or any other associated ocular disease. The absence of amblyopia was confirmed in preverbal children by the ability to maintain central steady fixation with each eye and among literate children, by the presence of visual acuity equal to or greater than 20/30 in each eye and equal visual acuity in both eyes.

All patients were examined by at least two investigators. Cover/uncover testing was used to diagnosis intermittent exotropia. Prism and alternate cover testing was performed with distance (6 metres) and near (33 cm) fixation targets in order to determine the magnitude of the exodeviation. Accurate fixation and accommodation were assured by having the patient identify different fixation targets as measurements were being obtained. Depending on the age and development of the patient, Snellen letters or Allen symbols were used as fixation targets. Ocular occlusion was not performed before obtaining the measurements noted above. When possible, confrontation visual field testing was performed to rule out hemianopic visual field deficits.

The charts were reviewed for the presence of associated ocular, neurological and systemic diseases. All patients and parents in the study and control groups were routinely questioned at each visit regarding the presence of neurological diseases including developmental delay, attention deficit disorder, and seizures. Most of the patients diagnosed with neurological disease were evaluated by a paediatric neurologist or a child development specialist before their ophthalmologic evaluation.

Statistical analysis
The prevalence of neurological disease and the sex distribution in the study and control groups were compared with a two tailed ² test. The age distribution in each group was compared with a two sample t test.

RESULTS
A total of 94 children had intermittent exotropia. Twenty eight children were excluded from the analysis. Reasons for exclusion included insufficient cooperation for accurate distance measurements (18 patients), an exodeviation at near that exceeded the deviation at distance by less than 10 prism dioptres (eight patients), strabismus surgery that was performed before evaluation by one of the investigators (one patient), and ocular motility measurements that were inconsistent (one patient).

The characteristics of the study and control groups are shown in table 1. The study and control groups did not differ significantly with respect to sex and age at evaluation. The 29 patients in the study group had intermittent exotropia that increased with near fixation with a mean deviation of 19 prism dioptres at distance and 35 prism dioptres at near. Seventeen of these 29 patients had an intermittent near deviation greater than or equal to 35 prism dioptres indicating robust fusional convergence amplitudes; 19 of these 29 patients (66%) had a history of concurrent neurological abnormalities as listed in table 2.

 
The control group consisted of 37 patients with a mean exodeviation of 30 prism dioptres at distance and 13 prism dioptres at near. Seven of these 37 patients (19%) had a history of concurrent neurological abnormalities as listed in table 2. The prevalence of neurological abnormalities was significantly higher in the patients who had an intermittent exotropia that increased with near fixation compared with the control group (p = 0.0002). Despite the significant difference in prevalence, the spectrum of neurological abnormalities was qualitatively similar between both groups.

DISCUSSION
We found a high prevalence of neurological disease in children with intermittent exotropia increasing at near fixation. Exodeviations that increase during near fixation have been associated with several neurological disorders including head trauma, dyslexia, Parkinson’s disease, congenital central hypoventilation syndrome, subdural haematoma, and stroke.^{3,4,5,6,7,8,9,10,11,12,13,14} The term "convergence insufficiency" has been loosely applied to this heterogeneous group of patients with exodeviations that become problematic during near fixation. In this context, apparent convergence insufficiency may arise from multiple mechanisms ranging from decreased fusional convergence amplitudes, a low accommodative convergence/accommodation ratio, accommodative insufficiency, poor convergence effort, poor accommodative effort, poor concentration, and pharmacological effects of medications.^{3,4,5,6,7,8,9,10,11,12,13,14} We are unable to assign a specific neurophysiological substrate to our study patients with intermittent exotropia that increases with near fixation. However, many of our study patients were able intermittently to fuse large exodeviations, demonstrating that their convergence amplitudes were greater than normal.

The magnitude of exodeviations at near is affected by accommodative and convergence effort. We encouraged accommodative and convergence effort by requiring our children to identify fixation targets as measurements were being obtained. However, we cannot exclude the possibility that reduced accommodative or convergence effort may have contributed to the high prevalence of exodeviations that increase with near fixation in children with neurological disease.

This study should be viewed in light of its inherent limitations. Firstly, because our cohort was gleaned from a children’s hospital population, our findings do not necessarily reflect the prevalence of neurological dysfunction in the general population. However, the increased prevalence of neurological disease in our children with intermittent exotropia that increases with near fixation compared with our control group of patients suggests that this association is real. Secondly, the prevalence of neurological disease was determined from a retrospective chart review. Not every patient was examined by a paediatric neurologist. However, patients and parents were routinely questioned regarding the presence of neurological disease at each visit. It is unlikely that a more detailed paediatric neurological evaluation would have disclosed clinically significant undiagnosed neurological disease in a significant number of our apparently healthy patients. Finally, we did not formally measure accommodative or convergence amplitudes in most of our patients with intermittent exotropia that increases with near fixation.

Our study confirms a high prevalence of neurological disease in children who have intermittent exotropia that increases with near fixation. However, no patient was subsequently found to have a serious treatable neurological lesion. As such, neuroimaging is not warranted, and further diagnostic evaluation can be guided by the clinical history. Although the determinants of increased near disparity in intermittent exotropia have yet to be defined, this form of strabismus appears to be a "soft" sign of neurological disease in children.

ACKNOWLEDGEMENTS
Supported in part by unrestricted grant from Research to Prevent Blindness and the Pat & Willard Walker Eye Research Center, Jones Eye Institute, University of Arkansas for Medical Sciences.

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