Incidence of Amblyopia and Its Risk Factors in Children With Isolated Metopic Craniosynostosis (click to read full article)

Objective: Ophthalmic abnormalities in children with syndromic craniosynostosis have been reported previously, and referral of these children to a pediatric ophthalmologist is recommended. However, it is not as clear whether a child with nonsyndromic synostosis needs to be referred to a pediatric ophthalmologist. The aim of this study is to report the incidence of amblyopia and its risk factors in children with isolated metopic craniosynostosis.
Design: An institutional review board–approved, retrospective review was performed on 91 children diagnosed with isolated metopic craniosynostosis. Ophthalmologic records were reviewed for diagnoses of amblyopia, strabismus, and refractive error.

Results: Of the 91 children, 19 (20.9%) had astigmatism, eight (8.8%) had amblyopia, eight (8.8%) had strabismus, five had myopia (5.5%), five had hyperopia (5.5%), and five had anisometropia (5.5%). The incidence of amblyopia and its risk factors found in our study are higher than the rate found in the clinically normal pediatric population.
Conclusions: In our patient population, children with isolated metopic craniosynostosis demonstrate an increased rate of amblyopia and its risk factors. Amblyopia is best treated early in life to achieve a successful outcome. A referral to a pediatric ophthalmologist for a formal eye exam and potential treatment is therefore recommended for children with isolated metopic craniosynostosis.

Craniosynostosis is a complex condition that involves prematurely fused cranial sutures and can occur in isolation or in association with a multitude of described syndromes (Mount and Dwelstad, 2007). In either case, management ideally occurs in the context of a dedicated multidisciplinary craniofacial anomalies team (McCarthy et al., 2012). Over the past several years, multiple studies have demonstrated an increasing incidence of metopic craniosynostosis compared with other types of synostosis (Selber et al., 2008; Di Rocco et al., 2009; Van der Meulen et al., 2009; Kweldam et al., 2011).

Ophthalmic abnormalities are known to be associated with isolated and syndromic craniosynostosis (Mount and Dwelstad, 2007). Referral to a pediatric ophthalmologist who is familiar with treating patients with craniosynostosis is recommended by the guidelines put forth by the Conference for Parameters of Care for Craniosynostosis (McCarthy et al., 2012). From an ophthalmologic standpoint, it has been recommended that evaluation for corneal and optic nerve complications be performed by a qualified ophthalmologist, that is, someone who is board certified and is a member of a craniofacial anomalies team that has experience in managing patients with craniosynostosis.

Specifically, recommendations include a diagnostic workup by an ophthalmologist within the patient’s first year of life with treatment as needed. Evaluating for ocular adnexa abnormalities, proptosis, corneal exposure, globe luxation, decreased vision, refractive errors, amblyopia, strabismus, and other ocular abnormalities is recommended. Subsequent ocular exams as the child grows are based on the conditions found initially and their severity (McCarthy et al., 2012).

To date, most studies on craniosynostosis and ocular findings are limited to the syndromic craniosynostosis population and/or are small case series with few patients (Hertle et al., 1991; Khan et al., 2003; Khong et al., 2006; Tay et al., 2006; Liasis et al., 2011). Patients with syndromic craniosynostosis generally have more severe ophthalmic complications than patients with nonsyndromic craniosynostosis (Newman, 1991; Persing, 2008). For instance, children with Crouzon syndrome can have proptosis and corneal exposure leading to visual loss. Evaluation for papilledema is also important as an indicator for increased intracranial pressure. Although there is consensus that children with syndromic craniosynostosis should be referred to a pediatric ophthalmologist, the need for referral of children with nonsyndromic craniosynostosis is not as clear. Differing recommendations have been made for referring patients with nonsyndromic craniosynostosis to a pediatric ophthalmologist (Persing, 2008; McCarthy et al., 2012).

Recently, MacIntosh and colleagues (2011) described the incidence of refractive error and strabismus in a large retrospective study of 64 patients with nonsyndromic metopic craniosynostosis. However, there are no reports regarding the incidence of amblyopia in patients with metopic craniosynostosis. Identifying amblyopia is important because it is the leading cause of vision loss in children (Van Noorden and Campos, 2002). Amblyopia treatment is most successful when begun early in life (Repka et al., 2014). The objective of our study was to report the incidence of amblyopia and its risk factors in addition to other ophthalmic findings in patients with isolated metopic craniosynostosis. To the best of our knowledge, this study is the largest to report ophthalmic findings in this population and the first to report the incidence of amblyopia in patients with isolated metopic craniosynostosis.

Methods

An institutional review board–approved, retrospective review was performed of all patients who were seen at our tertiary-care referral center between June 2007 and April 2013 and diagnosed with metopic craniosynostosis. In total, 112 consecutive patient records with a clinical diagnosis of metopic craniosynostosis and subsequent referral to pediatric ophthalmology were reviewed. Our practice is to refer all of our patients with craniosynostosis for a complete ophthalmologic evaluation. Children with a metopic ridge and no trigonocephaly or dysmorphology related to the metopic suture do not undergo the same evaluation and were not included in this study. Exclusion criteria were a history of syndromic diagnosis, primary ocular disorder, or systemic disorders with ophthalmologic sequelae; in addition, we excluded those who did not have an ophthalmologic examination after our recommendation was made.

During the period reviewed, 112 children were diagnosed with isolated metopic craniosynostosis. Of these, 15 were excluded because an ophthalmologic evaluation was lacking, two were excluded because of syndromic diagnosis (trisomy 18 and Dandy-Walker syndrome), three were excluded because of a history of primary ocular disorder (congenital glaucoma, retinopathy of prematurity, and Axenfeld-Rieger syndrome), and one was excluded because of systemic disorder (osteogenesis imperfecta). The remaining 91 children with isolated metopic craniosynostosis were studied: 57 boys and 34 girls ranging in age from 2 to 105 months old (mean = 20.21 months) at the time of their first ophthalmologic examination.

Records were assessed for the following data: sex; age at examination; visual acuity, including fixation preference; amblyopia; strabismus and binocular status; and refractive error. Collected orthoptic measures included extraocular motility; presence of manifest strabismus >8 prism diopters on cover test; and binocular sensory testing function as determined by the base-out prism convergence test at near, the Worth-4-Dot test, or the Titmus stereotest. Cycloplegic refraction was performed on all patients. Significant refractive error was defined as the American Academy of Ophthalmology (AAO) Preferred Practice Pattern age-adjusted targets: greater than 2.00 to 3.00 diopter (D) astigmatism, greater than +4.50 to +6.00 D hyperopia, greater than −3.00 to −5.00 D myopia, and greater than +1.50 to +2.50 D anisometropia.

Results

Of the 91 children, 19 (20.9%) had astigmatism, eight (8.8 %) had amblyopia, eight (8.8%) had strabismus, five had myopia (5.5%), five had hyperopia (5.5%), and five had anisometropia (5.5%) (Tables 1 and 2). In total, 22 children (24.2%) had a refractive error. Of the eight children treated for amblyopia, five had amblyopia caused by combined strabismus and refractive risk factors and three had purely refractive risk factors (Table 3).

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Discussion

Our study shows an increased incidence of amblyopia (8.8%) in our population of children with isolated metopic craniosynostosis compared with the general pediatric population rate of 1.5% to 1.8% (Multi-ethnic Pediatric Eye Disease Study Group, 2008; McKean-Cowdin, 2013). All of the children diagnosed with amblyopia in our study were treated with glasses and penalization therapy when indicated (part-time occlusion or atropine 1% twice weekly in the better eye). Surgical correction of strabismus was also performed when indicated. Amblyopia improved with treatment in all children.

Amblyopia is the leading cause of vision loss in children. Early identification and treatment of amblyopia is associated with better outcomes. A reported 85% to 90% of children can obtain 20/40 vision or better with successful treatment. However, because residual deficits are common, it is important to identify and treat amblyopia risk factors early in life (Beardsell et al., 1999; Flynn et al., 1999; Holmes et al., 2011). Given the higher incidence of amblyopia and amblyopia risk factors in this population, early referral to a pediatric ophthalmologist is recommended for those with isolated metopic craniosynostosis. We recommend that this ophthalmologic assessment be performed as soon as possible after a diagnosis of isolated metopic craniosynostosis is made because amblyopia and its risk factors are best treated early in life. Duration of the evaluation and treatment is determined by the ophthalmologist and depends on the abnormalities found.

Many of the previous studies regarding ocular findings in craniosynostosis have focused on syndromic craniosynostosis. To the best of our knowledge, none have studied isolated patients with metopic craniosynostosis and amblyopia in as large a sample size as in this study.

Furthermore, this study supports the findings of previously published reports of an increased incidence of strabismus and refractive error in children with isolated metopic synostosis. The incidence of strabismus in our population was 8.8%, which is lower than that found by MacInosh and colleagues (2011). Still, we found a higher incidence of strabismus than the 2.4% to 3.6% found in the general pediatric population (McKean-Cowdin, 2013). We found that 24.2% of our patient population had some type of refractive error compared with the study by MacIntosh and colleagues (2011), which found 28.13% with refractive error. In comparison, studies of the general pediatric population have shown a prevalence of 1.2% to 4% for myopia, 13.5% to 25.7% for hyperopia, and 6.3% to 8.3% for astigmatism (Wen et al., 2013). Myopia and astigmatism in our population, in particular, were higher at 5.5% and 20.9%, respectively. In an attempt to consider the process of emmetropization, during which infants undergo expected improvement in astigmatism and hyperopia, we have used the latest age-adjusted AAO targets (American Academy of Opthalmology Pediatric Opthalmology/Strabismus Panel, 2012). The increased incidence of refractive error amenable to treatment in our patient population is, in our opinion, another indication for early referral to a pediatric ophthalmologist.

This study is limited by its retrospective nature, lack of a control group, and single-center design. Although our study had no control group, we refer to previous large-scale studies on the rates of amblyopia, strabismus, and refractive error in the general pediatric population. Many children who were referred to our pediatric ophthalmologist ultimately were not brought to their appointments. In spite of this, our study population of 91 children is the largest study to date reporting amblyopia and its risk factors in isolated metopic craniosynostosis.

Conclusions

In our patient population, children with isolated metopic craniosynostosis were at increased risk for amblyopia, strabismus, and refractive error. Amblyopia and its causes are best treated early in life. Early referral to a pediatric ophthalmologist for a formal eye exam and potential treatment is therefore recommended for children with isolated metopic craniosynostosis.

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Footnotes

Dr. Nguyen is Resident, Division of Plastic Surgery, University of Missouri, Columbia, Missouri. Ms. Shock is medical student, University of Missouri Medical School, Columbia, Missouri. Dr. Missoi is Assistant Professor and Chief of Pediatric Ophthalmology, Department of Ophthalmology, University of Missouri, Columbia, Missouri. Dr. Muzaffar is Associate Professor and Director of Craniofacial and Pediatric Plastic Surgery, Division of Plastic Surgery, University of Missouri, Columbia, Missouri.

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