Anisocoria

The Problem

“One of my child’s pupils is larger than the other.”

Common Causes

Physiological anisocoria

Horner syndrome

Iritis

Pharmacological

Other Causes

Third nerve palsy

Trauma

Congenital iris anomalies

KEY FINDINGS

History

Physiological anisocoria Mild asymmetry

Variable (pupils sometimes equal) Horner syndrome

Pupils always unequal Worse in dim light

Ptosis on side of smaller pupil

Possible decreased sweating of face on affected side Unequal pupil color in congenital or early acquired cases Associated with some systemic disorders

Neuroblastoma

Thoracic or cervical surgery Birth trauma with cervical injury

Trauma

History of direct ocular injury Iritis

History of juvenile idiopathic arthritis Ocular pain, redness

Pharmacological

Exposure to topical medications or plants that affect pupil

Third nerve palsy Strabismus, ptosis

Systemic diseases associated with third nerve palsy

Examination

Physiological anisocoria

Difference between pupils less than 1.0 mm Variable, sometimes equal

Greater in dim light Horner syndrome

Asymmetry greater in dim light Mild ptosis on affected side

Possible unequal sweating on affected side Possible difference in iris pigment (heterochromia)

Trauma

Affected pupil may be smaller or larger than normal pupil Other signs of ocular trauma

Iritis

Pupil nonreactive, possibly irregular Possible cataract

WHAT SHOULD YOU DO?

Mild ( 0.5 mm) anisocoria in young children is usually normal, particularly if it is variable. Anisocoria associated with other disorders, particularly Horner syndrome

and third nerve palsy, is not an isolated finding. If a patient has ptosis along with anisocoria, referral to a pediatric ophthalmologist is indicated for evaluation of possible Horner syndrome or third nerve palsy. If the pupil does not react at all, referral is also indicated.

What Shouldn’t Be Missed

Horner syndrome, particularly in older children, may result from serious diseases such as neuroblastoma. These patients require evaluation to look for these problems. Children with iritis secondary to juvenile idiopathic arthritis (JIA) may have no symptoms of ocular discomfort despite severe inflammation. In some of these patients, abnormal pupils due to scarring of the iris may be the first abnormality noted.

COMMON CAUSES

1.Physiological anisocoria. Mildly asymmetric pupils may occur in otherwise normal infants. This may be familial. The anisocoria is more noticeable in dim light. The hallmark of physiological anisocoria is variability, with the pupils sometimes appearing equal. Physiological anisocoria does not cause any problems with development of vision.

2.Horner syndrome. Horner syndrome occurs due to interruption of the oculosympathetic chain that begins in the hypothalamus, travels through the spinal cord to the thorax, and ascends along the internal carotid artery to the orbit. Lesions anywhere along this pathway may cause Horner syndrome. The syndrome is characterized by anisocoria (pupil smaller on the affected side), mild ptosis, and anhidrosis (decreased sweating on the affected side of the face) (Figure 18–1). It typically does not cause vision problems. It is important because of its association with other systemic conditions.

3.Iritis. Most patients with iritis (intraocular inflammation) have marked eye discomfort and seek medical attention because of this complaint. For unknown reasons, children with iritis associated with JIA usually do not experience significant eye pain. Because of this, even severe inflammation may go

FIGURE 18–1 ■ Horner syndrome in a patient with neuroblastoma in the left lung apex. Note the smaller pupil and ptosis on the left.

CHAPTER 18 Anisocoria ■ 109

FIGURE 18–2 ■ Scarring of iris to anterior lens capsule in a patient with iritis.

unnoticed until substantial eye damage is present. Children with JIA sometimes present with nonreactive pupils due to scarring of the iris to the lens capsule (Figure 18–2).

4.Pharmacological. Several eye drops or exposure to certain plants may affect the pupil. This diagnosis can usually be established with a careful history, examination, and confirmatory drop testing (Table 18–1).

5.Trauma. Direct ocular injuries may result in damage to the muscles in the iris that control pupil size (Figure 18–3). In these patients, there is usually a recognized history of trauma.

6.Third cranial nerve palsy. Patients with third cranial nerve palsies usually have an enlarged pupil on the affected side, along with marked strabismus and ptosis. Congenital third nerve palsies

Table 18–1.

Pharmacological Causes of Anisocoria (Unilateral Topical Medication or Exposure)

■Affected pupil larger

Atropine

Scopolamine

Cyclopentolate

Tropicamide

Phenylephrine

■Affected pupil smaller

Pilocarpine

■Plant exposure (due to belladonna alkaloids—affected

pupil larger)

Jimsonweed

Moonflower

Black henbane Deadly nightshade

110 ■ Section 2: Symptoms

FIGURE 18–3 ■ Asymmetric pupil following trauma, with scarring of iris to anterior lens capsule (arrow).

Table 18–2.

Anisocoria With Affected Pupil Smaller

■Horner syndrome

■Physiological

■Trauma

■Inflammation

■Congenital third cranial nerve palsy (uncommon)

Table 18–3.

Anisocoria With Affected Pupil Larger

■Third cranial nerve palsy

■Pharmacological

■Trauma

■Inflammation

■Adie tonic pupil

sometimes present with a smaller pupil on the affected side. Partial third cranial nerve palsies present with variable ptosis and eye movement abnormalities, in which case the anisocoria is helpful in establishing a diagnosis (Figure 18–4).

APPROACH TO THE PATIENT

The presence of unequal pupils in children is concerning, primarily because this finding may result from serious underlying disorders. Most patients will be referred to an ophthalmologist. An appropriate evaluation can determine whether an underlying problem may be present and what additional investigations are warranted.

When the pupils are unequal, it is important to determine which pupil is abnormal. The iris sphincter muscles, which cause the pupil to become smaller, are under parasympathetic control. The iris dilator muscles, which cause the pupil to become larger, are under sympathetic control. If the abnormal pupil is smaller,

the anisocoria is usually worse in dim light, indicating a defect in dilation of the affected pupil (a sympathetic abnormality) (Table 18–2). If the affected pupil is larger, the anisocoria is usually worse in bright light, indicating an abnormality of constriction (a parasympathetic problem) (Table 18–3). If the pupil does not react at all, this usually indicates trauma, inflammation with scarring, or a pharmacological effect (Table 18–4).

History

Anisocoria may be brought to your attention by the patient’s parents, or it may be noticed during a wellchild evaluation. The history should include general questions about the child’s health and development, and a neurological review of systems should be obtained. A history of arthritis increases the likelihood that the child may have iritis with secondary iris damage.

General questions about the anisocoria should include when it was first noted, which pupil is bigger (or

smaller), whether the anisocoria is constant or variable, whether it is more noticeable in dim or bright light, and whether there has been any ocular trauma or exposure to medications or plants that could affect the pupils. More specific questions will be indicated based on the diagnoses being considered.

If Horner syndrome is suspected, questions should be asked about the child’s birth. Difficult deliveries may cause Horner syndrome due to damage to the cervical portion of the oculosympathetic chain (although most infants with Horner syndrome do not have such a history and the etiology of the problem is not known). Horner syndrome may also be caused by a number of disorders along the neural pathway, including lesions in the brain, chest, and neck. Neuroblastoma is a common cause of acquired Horner syndrome in children.

Anisocoria due to third nerve palsy is accompanied by ptosis and strabismus. This is usually readily distinguished from Horner syndrome (Table 18–5).

A

B

Examination

A general ocular examination should be included in the evaluation of children with anisocoria, including measurement of visual acuity using appropriate methods for age. The pupil reaction to light should be checked to be sure the iris constricts concentrically. The pupil size should be measured in dim light and bright light. Some unusual congenital iris abnormalities may present with abnormal pupils, including colobomas (Figure 18–5A), large iris nevi, heterochromia (unequal pupil color), congenital iris ectropion (Figure 18–5B), and persistent pupillary membranes (Figure 18–5C).

Children with physiological anisocoria have normal irises, the asymmetry is mild (usually <0.5 mm), and the anisocoria is more noticeable in dim light. The remainder of the examination is normal. The pupil asymmetry in Horner syndrome is also more noticeable in dim light. In children with congenital or

C

FIGURE 18–5 ■ Congenital iris anomalies causing abnormal pupil appearance. (A) Iris coloboma. (B) Congenital iris ectropion (ectropion uveae) (arrow). (C) Persistent pupillary membrane.

112 ■ Section 2: Symptoms

early-acquired Horner syndrome, the irises may have different colors.

If there is no pupillary reaction, the cause is likely pharmacological, trauma, or scarring of the iris due to iritis. Patients with complete third cranial nerve palsy also may have no pupil reaction. If the etiology is trauma, the child should be examined for other ocular and periocular injuries. If iritis is suspected, the child may also have a cataract. Because JIA is a common cause of iritis in children, an examination of the joints should be performed.

Additional ocular examination should include evaluation for ptosis and strabismus. The eyelid height, levator muscle function, and extraocular movements should be assessed. The presence of ptosis indicates that Horner syndrome or a third cranial nerve palsy is likely present. The ptosis in Horner syndrome is mild (1 to 2 mm), whereas marked ptosis is typical with third nerve palsies. Strabismus (with the eye out and down) also occurs in third nerve palsies (Figure 18–4 and Table 18–5).

pupil is abnormal (Figures 18–6, 18–7, and 18–8). If the pupil does not constrict at all, referral to an ophthalmologist is indicated. If anisocoria is accompanied by ptosis, the patient should be referred for evaluation of possible Horner syndrome or third cranial nerve palsy. If a diagnosis of acquired Horner syndrome is confirmed, an extensive evaluation is indicated to look for potential causes.

WHAT SHOULDN’T BE MISSED

Horner syndrome is one of the most common etiologies of nonphysiological anisocoria in children. If present from birth, it is usually benign, but urine vanillylmandelic acid may be measured to screen for neuroblastoma. Acquired Horner syndrome raises a significant concern for a serious underlying cause. Nonreactive pupils suggest the possibility of trauma or intraocular inflammation, which also requires prompt ophthalmic evaluation.

The Problem

“My child’s eye reflex looks white.”

Common Causes

Cataract

Retinoblastoma

Pseudoleukocoria

Other Causes

Retinal abnormalities

Detachment

Coat’s disease

Retinopathy of prematurity

Retinal coloboma

KEY FINDINGS

History

General

When first noticed? Getting worse?

Does the eye wander?

Does the child appear to see? Cataract

Family history of childhood cataracts Other systemic/developmental problems

Retinoblastoma

Family history of retinoblastoma Pseudoleukocoria

Only noticed in photographs when taken from the side

Retinal disorder Premature birth

Family history of retinal disease

Examination

General

Assessment of red reflex with direct ophthalmoscope

Vision Strabismus

Cataract Clouding of lens

Retinoblastoma

White mass posterior to lens Retinal detachment

Grey mass posterior to lens Pseudoleukocoria

Red reflex appears normal when viewed from straight ahead

Abnormal when viewed from side

WHAT SHOULD YOU DO?

Almost all patients whose parents report an abnormal red reflex should be referred to a pediatric ophthalmologist due to the potential serious implications of the possible diagnoses. Similarly, if the red reflex cannot be adequately visualized during a well-child examination, referral is indicated.

What Shouldn’t Be Missed

Retinoblastoma is highly curable if it is identified while confined to the eye, but is potentially lethal if it spreads. Therefore, early diagnosis is very important.

The visual prognosis for infantile cataracts is directly related to the age at which they are detected and treated. Unilateral congenital cataracts should be removed by 6 weeks of age to maximize the potential for vision.

COMMON CAUSES

1.Cataracts. Cataracts in infants are most commonly identified by an abnormal red reflex (Figure 19–1). Due to the high risk of amblyopia in unilateral cataracts, prompt referral to a pediatric ophthalmologist is indicated. Bilateral cataracts may occur in association with several syndromes or diseases, and these children require evaluation for these systemic disorders (see Chapter 30).

2.Retinoblastoma. Retinoblastoma is rare, but it is the most common primary intraocular tumor in children. It most frequently presents due to an abnormal red reflex (Figure 19–2A and B). It is one of the few life-threatening disorders encountered in pediatric ophthalmology. Intraocular retinoblastoma is very treatable, but the mortality for metastatic disease is high. Identification of tumors before systemic spread is critical. Most children with large unilateral tumors will require enucleation (surgical removal of the eye), but the eye and vision may sometimes be preserved if the tumors are identified when they are small.

3.Pseudoleukocoria. The optic nerve head at the back of the eye is white. If a light is shined into the eye from an oblique angle temporally, the reflection from the optic nerve head may fill the pupillary opening, producing pseudoleukocoria (Figure 19–3). This usually requires evaluation by a pediatric ophthalmologist to verify.

4.Retinal disorders. Retinal disorders that cause detachments are rare in children. They most commonly occur in infants with retinopathy of prematurity and may also occur following

FIGURE 19–2 ■ Retinoblastoma, left eye. (A) Abnormal red reflex.

(B) Magnified view shows vascularized elevated white retinal mass. The lens is clear.

FIGURE 19–3 ■ Pseudoleukocoria, left eye. The light reflex in the left eye appears white due to a reflection from the optic nerve head (which is white). Note that the photograph is taken from the patient’s left side.

116 ■ Section 2: Symptoms

Table 19–1.

Causes of Retinal Detachment in Children

■Retinopathy of prematurity

■Systemic diseases

Incontinentia pigmenti

Familial exudative vitreoretinopathy

■Trauma

■Toxocara

■Coat’s disease

trauma or due to rare familial disorders (Table 19–1). Large retinal colobomas may also produce leukocoria (Figure 19–4A and B). Toxocara infections may cause both retinal detachments and cataracts. They usually present as inflammatory white masses in the peripheral retina (Figure 19–5).

A

B

FIGURE 19–4 ■ Retinal coloboma. (A) Leukocoria secondary to reflection from abnormal retina. Note the small iris coloboma (arrow).

(B) Fundus examination shows large inferior retinal coloboma.

FIGURE 19–5 ■ Toxocara infection of the retina. These usually present as inflammatory white masses in the peripheral retina. Note the traction bands extending from the surface of the lesion (arrow).

APPROACH TO THE PATIENT

An abnormal red reflex is often the first abnormality noted in patients with potentially lifeand visionthreatening disorders. Many of these occur in infants and young children, who are unable to vocalize complaints. It is important to realize that in young children, even if one eye has extremely poor vision, as long as the other eye sees normally, the child will function well visually. Therefore, the absence of any complaints about the child’s vision in no way rules out the possibility of unilateral eye problems. Because of this, examination of the red reflex should be part of every routine wellchild check.

History

Parents may come in to the pediatrician having noted an abnormal red reflex, or it may be noted during a routine examination. In either setting, one should ask how well the child appears to see. If the family has noticed an abnormal red reflex, the age when it was first noted should be determined. If only one eye is affected, the child will usually appear to see normally. If a child has a bilateral disorder, abnormal visual behavior will often be the first symptom noted by parents. If a child has decreased vision in one eye for any reason, strabismus often develops. This may be either esotropia or exotropia, and is often intermittent.

Questions about the child’s general health may raise the suspicion of syndromes that may be associated with cataracts. Premature birth may lead to retinopathy of prematurity, which may cause retinal detachments. Retinoblastoma, cataracts, and many retinal disorders may be inherited, and therefore obtaining a family history is important.

FIGURE 19–6 ■ Red reflex examination. This is most easily performed by using the direct ophthalmoscope from 2 to 3 feet away from the patient in a dim room. The examiner focuses on the child’s face with the ophthalmoscope, and the red reflex can be compared between the two eyes.

Examination

The child’s vision and examination of the anterior segment should be performed in the normal manner. To best evaluate the red reflex, use the direct ophthalmoscope from 2 to 3 feet away from the patient in a dim room. Focus the ophthalmoscope on the patient’s face. The red reflex can then be assessed and compared between the two eyes (Figure 19–6). The symmetry of the corneal light reflexes can also be noted at this time to screen for strabismus. Pseudoleukocoria, retinoblastoma, and retinal colobomas usually cause a very white reflex, whereas retinal detachments are typically gray. The appearance of cataracts is highly variable. If a parent reports an abnormal red reflex, but it is not noted when shining the light into the patient’s eyes from straight ahead, you should assess the red reflex as you move the direct ophthalmoscope from side to side. Tumors of the nasal retina, for instance, may not be noted until the light is shined into the eye from a lateral position (Figure 19–7A–D). This may be difficult to differentiate from pseudoleukocoria, which is also only noted when viewed from a lateral position.

PLAN

If a parent reports an abnormal red reflex or if you note this on examination, the child should be referred promptly to a pediatric ophthalmologist. This is particularly important for retinoblastoma, which may be lethal if it spreads beyond the eye. If an abnormal red reflex is found on a newborn screening, the patient should also be referred promptly. In a newborn, a cataract is the most likely etiology for leukocoria. If an infant has a unilateral cataract, surgical removal should be performed in the first 6 weeks of life to maximize the visual potential.

CHAPTER 19 Abnormal Red Reflex ■ 117

A

B

C

D

FIGURE 19–7 ■ Leukocoria due to nasal retinoblastoma, left eye.

(A)Red reflex appears normal when viewed from straight ahead.

(B)Crescent-shaped abnormality (arrow) begins to appear when light is moved to left. (C) Red reflex absent as light moved further to left.

(D)Fundus examination reveals a large tumor filling the nasal retina. The optic nerve is marked by an arrow.

WHAT SHOULDN’T BE MISSED

Cataracts and retinoblastoma both often present with leukocoria. These are among the most treatable potentially visionand life-threatening disorders in pediatric ophthalmology, and early referral is critical (Figure 19–8).

When to Refer

■Any child with an abnormal red reflex should be referred to a pediatric ophthalmologist