Hospital for Sick Children's, The: Atlas of Pediatric Ophthalmology & Strabismus, 1st Edition

Ocular Manifestations of Systemic Disease



Alex V. Levin

Thomas W. Wilson

  1. Raymond Buncic

The craniofacial disorders are characterized by malformation of the cranial vault and/or facial bones. Premature fusion of one or more sutures, known as craniosynostosis, results in myriad congenital syndromes that are distinguished not only by the involved sutures and appearance of the head and face, but also by the presence and absence of other systemic findings. The genes involved in craniofacial development may also be involved in the formation of other body parts. Clefting abnormalities are a group of disorders that are the result of incomplete closure of the face and branchial clefts as defined by the Tessier clefting system. One must also distinguish between primary craniofacial malformations and the secondary deformations such as positional plagiocephaly.

Craniofacial disorders often have ophthalmic manifestations. A multispecialty team approach is required for the care and treatment of these patients. Significant vision loss can be observed due to primary coexisting malformations such as optic nerve hypoplasia, secondary effects of the disorder such as corneal exposure due to exorbitism or strabismic amblyopia, and complications of treatment such as hemorrhagic conjunctival prolapse following a bicoronal flap for surgical intervention.



Figure 14.1 Metopic Synostosis

Metopic craniosynostosis (trigonocephaly) is due to premature closure of the metopic suture of the skull. This causes a wedge-shaped malformation of the frontal bone, which leads to hypotelorism and pseudoesotropia. Increased intracranial pressure is rare. This is usually an isolated anomaly that does not affect cognition but may result in significant departure from a normal appearance.


Figure 14.2 Coronal Synostosis

Coronal craniosynostosis (anterior plagiocephaly) is due to premature closure of the coronal suture. This three-dimensional reconstruction of the skull shows premature closure of the right coronal suture. Note the posterior displacement of the superior and superolateral orbital rim, sometimes referred to as the “owl eye” or “harlequin orbit.” Bilateral coronal synostosis may also. Although often associated with other abnormalities of the skull or body, unilateral or bilateral coronal synostosis may also occur as an autosomal dominant condition due to mutations in the fibroblast growth factor receptor gene FGFR2 at 10q26. Elevated intracranial pressure may be present, particularly in bilateral cases.


Figure 14.3 Coronal Synostosis

Due to the superior and superolateral orbital rim recession, patients with coronal synostosis (anterior plagiocephaly) appear to have a recessed forehead on the affected side and pseudoproptosis. Misdiagnosis as buphthalmos (Chapter 10: Glaucoma, Fig. 10.1), contralateral hemifacial atrophy, or contralateral ptosis is not uncommon. The view from above (bottom image) is very useful in evaluating patients with craniofacial disorders and in this case immediately reveals the diagnosis.


Figure 14.4 Coronal Synostosis

Approximately 50% of patients with anterior plagiocephaly will have a vertical and/or horizontal strabismus with limited eye movements. This child has limited supraduction in abduction and eye movements consistent with bilateral inferior oblique overaction. This abnormal pattern may be associated with absent or malpositioned eye muscles, particularly in bilateral cases. Astigmatism is more common on the involved side(s).




Figure 14.5 Sagittal Synostosis

Sagittal synostosis (scaphocephaly) is due to premature closure of the sagittal suture. The skull is elongated in an anterior posterior direction. Often, there will be a palpable ridge along the fused suture and the anterior and posterior fontanelles will be completely or partially closed. Increased intracranial pressure is not uncommon and papilledema is the major ocular sign. Until cranial vault reshaping is performed, periodic ocular examination is suggested.


Figure 14.6 Exorbitism

In the multiple craniosynostosis syndromes the orbit is relatively shallow, leading to prominence of the globe. This is different than proptosis in which there is something (e.g., tumor) pushing the globe forward. Exorbitism can result in spontaneous and recurrent subluxation of the globe. Severe exorbitism can result in the lids being positioned behind the equator. Exposure keratopathy is a particular concern. Although subluxation may be treated by firm gentle pressure to reposit the globe in the orbit, craniofacial surgery is required for a more definitive result.


Figure 14.7 Complicated Exorbitism

Severe exorbitism can lead to conjunctival edema and corneal exposure, particularly if the eye becomes trapped anterior to the orbital rim, as seen here. Compromise to the optic nerve may occur. If the eye cannot be manually reposited within the orbit, treatment of this patient acutely would involve aggressive lubrication of the conjunctiva and cornea. Tarsorrhaphy is very difficult unless the eye can be placed back in the orbit. This patient required urgent advancement of the orbital bones.




Figure 14.8 Multiple Craniosynostosis Strabismus

The most common strabismus is a V-pattern exotropia with hypertropian adduction. Extraocular muscle anomalies are common and lead to strabismus. Anomalies include absent or malpositioned muscles with atypical insertion sites. Satisfactory surgical management of this strabismus is difficult. The elevation in adduction and V pattern might suggest an overaction of the inferior oblique muscles (Chapter 1: Strabismus, Figs. 1.28, 1.31, and 1.38), but the mechanism is most likely more complex. This pattern has been observed even in children with multiple craniosynostosis, exorbitism, and absent inferior oblique muscles.


Figure 14.9 Apert Syndrome—Strabismus

This child with the multiple craniosynostosis syndrome, Apert syndrome, shows significant exorbitism (Fig. 14.6) and strabismus. Syndactyly of the fingers and toes is a characteristic of Apert syndrome. The child has a large-angle right exotropia and hypotropia. This picture was taken in upgaze. Note the deficient elevation in both eyes, more so on the right. This may be due to anomalous or absent extraocular muscles. The patient is at risk for developing exposure keratopathy and amblyopia. Patching therapy is difficult due to the risk of corneal abrasion from the patch. This patient most likely will need advancement of the orbital bones. Following this surgery, strabismus surgery can be considered.




Figure 14.10 Apert Syndrome—Anomalous Muscles

Coronal computed tomography scan (left image) of the orbit shows malposition of the extraocular muscles. The superior rectus muscles are displaced temporally and the inferior rectus muscles are displaced medially. The long white lines bisect both muscles. It is difficult to predict the effects of such muscle aberrations and the appropriate strabismus surgery to correct strabismus if present. Exorbitism itself is also associated with excyclotorsion (Fig. 14.12), making it important to distinguish true anomalous location of the muscles versus rotation of the entire globe. The right image shows, intraoperatively, the absence of the inferior rectus muscle, which should have been located at the left (posterior) arm of the caliper.


Figure 14.11 Apert Syndrome— Syndactyly

Apert syndrome is the combination of multiple craniosynostosis and severe bony and cutaneous syndactyly. It is an inherited autosomal dominant disorder due to a mutation in the fibroblast growth factor receptor gene (FGFR2) at 10q26. The head is brachycephalic and may be turricephalic. There is marked hypoplasia of the midface with a prominent nose and hypertelorism. The ears are typically low set. Palate and dental abnormalities are common. This patient has already had several operations on his hands to attempt to convert what was complete five-digit syndactyly to a more functional hand. Crouzon syndrome, also due to mutation in FGFR2, is very similar to Apert but with normal hands.


Figure 14.12 Apert Syndrome— Excyclotorsion

This fundus photograph shows significant excyclotorsion of the right eye. The fovea is well below the horizontal meridian of the optic nerve. Patients with multiple craniosynostosis and exorbitism frequently have this sign. Excyclotorsion can be the result of mal- position of the recti muscles (Fig. 14.10) or the anomalous orbital structure. The excyclotorsion is usually bilateral and rarely results in symptoms. Stereopsis can still be maintained in many of these children and surgical correction for asymptomatic excyclotorsion is not advised.




Figure 14.13 Clover Leaf Skull

Kleeblattschädel (“clover leaf skull”) is a head shape that is due to synostosis of all sutures except the squamosal. The resulting head shape is characterized by a towering vertex of the head and temporal bulging (“trilobate skull”), as demonstrated in this image. The head shape is not a syndrome alone but is seen in a variety of multiple craniosynostosis syndromes including Apert and Crouzon. It is associated with hydrocephalus, which is the major cause of morbidity. Exorbitism can be quite profound (Figs. 14.6 and 14.7). Globe subluxation and corneal exposure are common.


Figure 14.14 Treacher-Collins Syndrome

Treacher-Collins syndrome (mandibulofacial dysostosis) is an autosomal dominant craniofacial abnormality of structures derived from the first branchial arch. Facial features include malar hypoplasia, triangular-shaped face, mandibular hypoplasia, and ear anomalies including deafness. There is a characteristic downslanting of the palpebral fissures with a sharply angular lower lid coloboma (Fig. 14.16). The disorder is bilateral. Exposure of the cornea becomes an increasing problem with age.


Figure 14.15 Treacher-Collins Syndrome

This profile view demonstrates the severe mandibular hypoplasia with microretrognathia. The ear has been partially reconstructed but the child has severe hearing loss and requires a bone conducting hearing aid. Oblique astigmatism is common but the wearing of spectacles can be a challenge if severe microtia or other ear anomalies are present. Until reconstruction is completed, glasses can be affixed to a head band worn over the cranial vault. This disorder is due to mutations in the treacle gene (TCOF1) at 5q32-33.1.


Figure 14.16 Treacher-Collins Syndrome—Lower Lid Coloboma

Patients with Treacher-Collins syndrome have a characteristic sharply downslanting lower lid coloboma with absent lashes and often an absent or otherwise anomalous lower lid puncta. The lateral edge of the coloboma rises acutely back to the normal lateral aspect of the lid margin. The lid aperture takes on a trapezoidal configuration. The lacrimal drainage system may be anomalous and dysfunctional or completely absent, but the superior puncta are often present and functional. Chronic tearing and discharge usually do not appear until later in childhood. The palpebral fissure shortens horizontally with forced lid closure. This is secondary to absence or laxity of the lateral canthal tendon.




Figure 14.17 Binder Syndrome

Binder syndrome (maxillofacial dysplasia) is a developmental abnormality of the anterior maxilla and nose. Clinical features include a flat vertical nose and hypoplasia of the upper jaw and midfacial structures. Perhaps the most characteristic feature is the absence of the anterior nasal spine on radiographs. Hearing abnormalities may necessitate the use of a hearing aid, as seen here. Ocular manifestations may include strabismus, refractive error, exorbitism, and ptosis. Anomalous eye muscles have not been reported, unlike other multiple craniosynostosis syndromes.


Figure 14.18 Goldenhar Syndrome

Goldenhar syndrome is a subset of the oculo-auriculo-vertebral spectrum, disorders caused by abnormal development of tissues derived from the first branchial arch. Goldenhar syndrome is characterized by mandibular hypoplasia and hemifacial microsomia. Preauricular tags and an abnormal external ear are common (right image). The findings may be unilateral or bilateral. One ophthalmic abnormality, shown in the left image, is upper lid coloboma, usually involving the medial upper lid, with or without adhesion to the surface of the eye. This child's coloboma, particularly of the left upper lid, demonstrated the characteristic rectangular defect.


Figure 14.19 Goldenhar Syndrome—Limbal Dermoid

Limbal dermoids are round or oval opaque white masses attached to the cornea and sclera. They consist of surface ectoderm–derived tissue and may contain hair and sweat glands. These lesions are classified as choristomas. They are most commonly located at the inferotemporal limbus but may also occur on the conjunctiva or central cornea. Astigmatic or occlusion amblyopia is a concern. Surgical intervention usually involves peripheral lamellar or full-thickness keratopathy. Limbal dermoids are most frequently seen as part of Goldenhar syndrome.




Figure 14.20 Goldenhar Syndrome—Lipodermoid

Subconjunctival lipodermoids are most commonly found in the temporal orbit presenting as a smooth, pink, congenital, nonprogressive mass hugging the globe most often over the lateral rectus muscle. A few cilia are rarely present. The lipodermoid may encase recti muscles and intercalate themselves between the muscle fibers with or without an effect on eye movement. Surgical intervention is largely designed to address abnormal appearance. Deep dissection is therefore not recommended because inadvertent injury to the muscle with incomitant strabismus may occur.


Figure 14.21 Goldenhar Syndrome—Caruncle

Some patients with Goldenhar syndrome will have an absent or an abnormal caruncle. The caruncle may be enlarged, hypoplastic, or bilobed. In this child, the caruncle appears as an ectopic mass in the medial palpebral conjunctiva of the lower lid (arrow). Ectopic caruncle is often associated with lateral displacement of the lower lid puncta with or without nasolacrimal duct dysfunction. Although an abnormal caruncle has no effect on vision, it is a marker for an increased frequency of abnormalities of the ipsilateral nose and nasal cavity in Goldenhar syndrome.


Figure 14.22 Oculo-auriculo-vertebral Spectrum— Duane Syndrome

All forms of oculo-auriculo-vertebral spectrum, including Goldenhar, Wildervanck, and Klippel-Feil syndromes, may be associated with Duane syndrome (Chapter 1: Strabismus, Figs. 1.59, 1.60, 1.61, 1.62 and 1.63), usually type I Duane. There may be ipsilateral ear abnormality and hearing loss. This patient is attempting to look to his left. Notice the narrowing of the palpebral fissure on adduction of the right eye and absence of left eye abduction. The child has bilateral type III Duane syndrome in association with bilateral Goldenhar syndrome.


Figure 14.23 Fibrous Dysplasia

Fibrous dysplasia of the orbit is a disorder where excess osteoblastic activity results in fibrous replacement of bone. Virtually any bone in the body can be affected including the cranial vault, often involving the orbital bones. There are four forms: Monostotic, polyostotic, craniofacial, and cherubism. The craniofacial form is nonhereditary and typically unilateral, and most commonly affects the orbital roof and frontal and sphenoid bones, leading to downward displacement of the eye, proptosis, and extraocular muscle movement restriction, as shown here. Fibrous dysplasia usually is self-limiting, although orbital reconstruction is reserved for severe cases. Optic nerve compression may occur and requires urgent decompression of the optic canal.




Figure 14.24 Fibrous Dysplasia

Fibrous dysplasia is diagnosed by radiologic imaging, which demonstrates the excess fibrous stromal replacement of bone. The left image shows dramatic involvement of the clivus (arrow) with impending compression of both optic nerves. The three-dimensional reconstruction of the orbital roof, in the right image, shows infiltration of the bone with mass lesion on the left extending over to the right side as well. This patient had limited elevation of the left eye and proptosis.


Figure 14.25 Anterior Encephalocele

Encephaloceles are caused by defects in the cranial bones with herniation of dura with or without brain tissue. The brain tissue within the encephalocele may be dysplastic. Encephaloceles can occur in different locations, including the other two common locations: Occipital and basal. In the latter circumstance, the patient may demonstrate a notch in the upper lip and morning glory disc (Chapter 9: Optic Nerve, Fig. 9.5). Hypertelorism results from displacement of the orbits laterally as the orbital angle cannot be reduced due to the intervening brain during embryogenesis. Craniofacial and neurosurgical correction are necessary.


Figure 14.26 Anterior Encephalocele

This child has no brain tissue within the encephalocele, as demonstrated by the marked transillumination. The ocular effects of anterior encephalocele, in addition to the hypertelorism (Fig. 14.25), include amblyopia due to obstruction of the visual axis, and strabismus. Ocular malformations may also occur, including bilateral optic nerve hypoplasia or coloboma and bilateral microphthalmia.




Figure 14.27 Frontonasal Dysplasia

When there are more extensive midline defects, often including the nose, which may have a midline furrow indicating incomplete midline formation (left image), the term frontonasal dysplasia is used. Brain anomalies such as callosal agenesis may be associated. The right image illustrates a large encephalocele herniating through the ethmoid and sphenoid sinuses into the nasal cavity and the resulting severe hypertelorism. Should craniofacial surgery require intubation of the nasolacrimal system, the ophthalmologist must be cautious about intranasal manipulation. Other associated ocular findings may include strabismus (left image), optic nerve hypoplasia or coloboma, and microphthalmia.


Figure 14.28 Hypotelorism

Hypertelorism and hypotelorism refer to abnormalities in the distance between the anterior medial orbital rims as opposed to telecanthus, which refers to the soft tissues. Patients with hypotelorism may have associated abnormalities of the brain including holoprosencephaly and the absence of a separation and distinction between the two cerebral hemispheres. Holoprosencephaly is due to a mutation in the Sonic Hedgehog gene. Phenotypic variation ranges from fatal holoprosencephaly with a proboscis below a cyclopean eye to a normal craniofacial structure with the only abnormality being a single upper incisor.


Figure 14.29 Lateral Facial Dysplasia

The lateral facial dysplasias are a group of nonprogressive craniofacial malformations characterized by abnormal asymmetry of the facial structures, often including hemifacial atrophy. Associated ophthalmic anomalies include ipsilateral optic nerve hypoplasia and microphthalmia. The eye on the affected side may also appear enophthalmic and may have restrictions of eye movement (right image, patient looking to her left) and anterior segment abnormalities. In the left image, note also the deviation of the nose and the abnormal ear.


Figure 14.30 Amniotic Bands

Facial clefting can also occur in nonanatomic planes due to amniotic bands. These bands are felt to be due to rupture of the amniotic sac during development. The bands inhibit normal growth and lead to cleftlike syndromes. Significant facial and other developmental abnormalities can occur. Digits or limbs may be amputated or show significant constriction from the intrauterine effect of these bands.