Part 2: Disorders of the Eye

INTRODUCTION

Ocular trauma is a frequent presenting complaint and a major cause of ocular morbidity and unilateral blindness in children. The magnitude of serious eye injuries in children has been estimated at 11.8 per 100,000 per year. Children in the 11- to 15-year age group have a higher incidence of trauma compared to other age groups. Boys outnumber girls approximately 3 or 4 to 1.

Ocular injuries require prompt evaluation and care in order to preserve vision. Evaluation of the injury is more difficult due to decreased cooperation and understanding in children. The injured patient is frequently young, afraid, in pain, and able to provide only limited compliance. The examination should be as complete as the injury permits; forcible evaluation may risk further damage. Topical anesthesia, local anesthesia, and sedation are all useful for assessing and treating minor trauma. If the pediatrician or emergency room physician cannot perform an adequate examination, or as soon as there is concern for significant ocular damage, the injured eye should be covered with a protective shield (not patched) and ophthalmology consultation should be obtained. It is also important to recognize that managing the eye injury always takes a lower priority than managing life-threatening injuries and serious head trauma. The injured eye can be shielded while emergency procedures are under way to stabilize the child systemically. Yet, with the exception of the uncommon vasovagal response induced by eye examination, the ophthalmologist can conduct a limited brief assessment that will be relatively noninvasive and may offer helpful management guidelines. While that examination is pending, the eye should be shielded (not patched).

CORNEAL ABRASION

Corneal abrasion is one of the most frequent ocular injuries of childhood. The abrasion results from mechanical removal of the superficial epithelial layers of the cornea. This can cause intense pain, protective spasm closure of the lids, tearing, and photophobia, although some children may be surprisingly asymptomatic. Examination is facilitated by a drop of topical anesthetic followed by fluorescein dye. The dye is available as a liquid mixed with anesthetic or in dry impregnated strips. The latter tends to be more effective in diagnosis, as it allows only a small amount of dye to be placed. The strip must be wet with a drop of liquid (water, normal saline, Ringer’s, etc) and then gently touched briefly to the pink palpebral conjunctiva lining the inside of the lower lid or the bulbar conjunctiva on the white of the eye. The fluorescein will define the extent of epithelial cell loss when examined with cobalt blue illumination (blue light on direct ophthalmoscope or Woods lamp; Fig. 573-1).

Use of a cycloplegic agent and topical antibiotic ointment will provide comfort and prevent infection. The placement of a pressure patch to close the eyelid and promote healing of the epithelium was traditional care for children and adults, but more recent studies indicate that the patch may not increase the rate of healing or comfort. Younger children may resist or remove the patch. Normal eye closure during sleep will usually be enough to promote a rapid recovery. Corneal abrasions typically are healed within 1 to 2 days. Patients are generally examined within 24 hours to monitor healing, particularly if the abrasion is large or central. Small abrasions away from the visual axis do not necessarily need follow-up if the child is asymptomatic and the eye is not injected after 2 to 3 days. Secondary infection is rare except in those who wear contact lenses. Any child wearing a contact lens who presents with a red or painful eye should have the contact removed immediately. The dye can then be applied. If a corneal abrasion is found, the child should be referred promptly to an ophthalmologist. If there is a white area at the site of the fluorescein staining, this may indicate an infectious ulcer. The pediatrician should not treat, but should refer the child immediately, as the ophthalmologist may choose to culture the area; the results of culture may be useless after prior antibiotic treatment. Never patch those who wear contact lenses, as there is evidence that it may increase the risk for secondary infection in these patients.

THERMAL INJURIES

Thermal burns of the cornea from cigarette ashes, match heads, and other combustible materials are usually not serious, but when they are, the ocular surface and lid margins may be destroyed with little hope for salvageable vision. The rapid eyelid-closure reflex and Bell phenomenon (upward movement of the globe when threatened) usually limit the extent of the burn. Children burned in house fires or accidents usually sustain minimal, if any, corneal injury unless they were rendered unconscious by smoke inhalation or the eyes were abusively forced open. Cigarette burns of the cornea are the most common thermal injury to the ocular surface in childhood. The majority of these injuries occur in 2- to 4-year-old children, and they are usually sustained accidentally when a toddler runs into a cigarette held at eye level by an adult. The treatment is generally the same as for corneal abrasions. When the mechanism of thermal injury involves high-velocity impacts such as a firecracker, explosives, or firearms, it is critical to look for embedded foreign bodies on the eye or the surrounding orbital tissue and signs of open globe injury.

RADIATION BURNS

Ultraviolet light from unprotected sun exposure, sunlamps, snow reflection, and welding arcs can produce a diffuse superficial punctate keratitis (many pinpoint corneal abrasions) of the cornea that is extremely painful. The patient will present with a combination of pain, foreign-body sensation, tearing, photophobia, and blepharospasm. The findings are similar to those found with corneal abrasion except that there may be a delay from the exposure to the time the child becomes symptomatic. Treatment consists of broad-spectrum antibiotic ointment (eg, erythromycin, polysporin), consideration for cycloplegia, and patching for comfort and to promote healing. The epithelium heals over 24 to 48 hours, and there are usually no permanent sequelae. Those who wear contact lenses can also sustain this injury and require special treatment as discussed above.

Unprotected sun exposure can also cause damage to the retina, specifically the photoreceptors and the retinal pigment epithelium, known as solar retinopathy or solar maculopathy. Common symptoms include decreased vision and presence of a central scotoma. There are some reported cases in children caused by direct viewing of a solar eclipse. Solar retinopathy causes persistent damage to multiple retinal layers, despite good vision recovery.

Over the last few years, injuries involving accidental or intentional laser pointer exposure resulting in retinopathy have been increasing. Due to improving technology, laser pointers are becoming more powerful, and those that are manufactured outside of the United States often do not conform to the Food and Drug Administration (FDA) regulations. In addition, with the emergence of online marketplaces, these devices are becoming more readily available than before. The mechanism of injury typically involves staring directly at the laser pointer beam or at a laser pointer beam reflected off a mirror. Children are especially susceptible from accidental laser pointer exposure, because of their inability to read the warning labels and close resemblance of the light emitted from a laser pointer to the lights from toys. Current FDA regulations on general consumer class of laser pointer require a power less than 5 mW and a wavelength between 400 and 700 nm. Many reported cases of injury are from laser pointers with power outputs that are much higher than the FDA regulation. Shorter wavelength lasers are more damaging to the retinal tissue. For example, a green laser pointer would potentially be more damaging compared to a red laser pointer. The location of retinal damage is similar to that seen in solar retinopathy, at the level of the retinal pigment epithelium and outer retina. The power and duration of laser exposure are 2 main factors that determine the severity of the injury. Injuries can range from scarring of the retinal pigment epithelium to subretinal hemorrhage and retinal edema. If there is acute vision loss from suspected laser pointer exposure, it is essential to make a prompt referral to ophthalmology.

CHEMICAL BURNS

Treatment for chemical burns should be started immediately once the history of exposure is obtained. Acid burns are less serious than alkali burns, because acid precipitates proteins and results in a barrier to further penetration. In contrast, alkaline agents (eg, lye, cement, oven cleaner) activate collagenases, which may produce corneal liquefaction and ulceration, possibly leading to full-thickness perforation. Alkali burns may also cause an increased intraocular pressure secondary to contraction of the sclera and damage to the trabecular meshwork.

When the eye has been exposed to chemicals, begin copious irrigation with water or isotonic saline for 20 to 30 minutes. Use of a topical anesthetic and lid speculum will provide more comfort and permit thorough irrigation under the lids, but one should not wait to acquire these items if there is likely to be any delay. Effectiveness of irrigation is checked by assessing the pH of the tear film 5 to 10 minutes after installation. Irrigation should be continued until a neutral pH of 7.0 is attained or, in unilateral exposure, until the pH of the affected eye is equal to that of the unaffected eye. Normal tear film pH is 7.3 to 7.7. It is critical to never use acidic solutions to neutralize alkali exposure, or vice versa, because this could induce secondary chemical and thermal injuries. The volume of irrigation fluid required may vary from a few liters to over 10 liters.

Intravenous tubing (with the needle removed) attached to an irrigation solution may be used to irrigate over the cornea and under the lids to effectively remove contaminants and neutralize the tear film. Commercial irrigation devices such as the Morgan lens permit a contact lens attached to irrigation tubing to be placed over the cornea and under the lids. This provides comfortable, extended, hands-free irrigation. Placement of a topical anesthetic drop should be applied periodically for comfort.

Chemical burns can cause changes that range from superficial punctate staining to complete sloughing of the corneal epithelium. Severe chemical burns may produce pronounced chemosis, conjunctival ischemia, corneal edema and opacification, and anterior chamber inflammation. Treatment after irrigation consists of removing all particulate debris, including sweeping the fornices with a moistened cotton-tip swab; administering cycloplegia or topical antibiotic ointment; pressure patching; and, if needed, giving oral analgesics, glaucoma medications, and topical corticosteroids (use cautiously). Urgent ophthalmology consultation is suggested but not until the irrigation procedure is completed. The long-term management of severe burns may involve lysis of conjunctival scars (symblephara), application of collagenase inhibitors, conjunctival or corneal transplantation, and dry eye management.

FOREIGN BODY OF THE CONJUNCTIVA AND CORNEA

When faced with an apparent superficial ocular foreign body, several considerations are useful before attempting to remove it. Any history of high-velocity exposure (metal striking metal), the presence of associated conjunctival hemorrhage, or a foreign body overlying an oval- or teardrop-shaped pupil may indicate globe penetration with an intraocular foreign body. In such cases, urgent ophthalmology consultation is indicated, and the pediatrician should not attempt to remove the object. Complete ocular examination is frequently necessary and includes a careful exploration of the wound(s), a dilated fundus examination, and a possible computed tomography (CT) scan to exclude the presence of an intraocular or intraorbital foreign body.

Superficial conjunctival foreign bodies are usually removed by flushing the eye with isotonic saline or using a moistened cotton-tip applicator. Eversion of the upper lid is necessary if a foreign body is not readily located, especially if there are linear vertical fluorescein stain lines on the superior cornea. Topical anesthetic installation will facilitate the examination and foreign-body removal. The dye will also pool around a foreign body and thus aid in its identification. Eversion of the upper eyelid can be performed by having the patient look down while placing a cotton-tip or other blunt object against the lid crease. At the same time, the lid margin and tarsal plate are elevated by pulling upward with the lashes.

Corneal foreign bodies generally cause more pain than conjunctival foreign bodies. If the foreign body cannot be removed by irrigation, referral to an ophthalmologist is advisable unless the pediatrician/emergency physician is comfortable with proper foreign-body removal techniques using a slit lamp. After removing a foreign body, there is usually an associated corneal epithelial defect. Topical broad-spectrum antibiotic therapy is recommended for 2 to 4 days. All patients should be examined in 24 hours to rule out early corneal infection. Metallic foreign bodies may leave a localized rust stain. This may have to be removed by an ophthalmologist using a slit lamp.

EYELID LACERATIONS

Lacerations involving the eyelid margin or nasolacrimal system should be treated by an ophthalmologist. Other indications for referral to an ophthalmologist include ptosis, full-thickness laceration, missing tissue, and any concern about globe injury. Careful ophthalmic primary closure can help to prevent permanent notching of the eyelid margin, chronic tearing, trichiasis (inward turning of the eyelashes), or scarring of the nasolacrimal drainage system. Canalicular injury may not be recognized initially but should be suspected in medially located lid lacerations, especially those caused by dog bites or by catching the lid on a hook or other object. Lateral displacement of the papilla on which the puncta normally sits is a worrisome sign that the canaliculus has been severed. An examination under anesthesia may be necessary to define the extent of injury more definitively. To repair a severed canaliculus, the ophthalmologist may place a silicone stent at the time of anesthesia.

Full-thickness perforation of a lid, recognized by an external puncture wound that is also visible on lid eversion, is a high-risk indicator for orbital, globe, or brain (upper lid) injury. CT scan is recommended.

CONJUNCTIVAL LACERATIONS

All but the largest conjunctival lacerations can be managed without surgical repair. Most will heal spontaneously within a few days. Lacerated conjunctiva will stain with fluorescein dye as described above for the diagnosis of corneal abrasion. Application of topical antibiotic ointment, with or without a pressure patch, constitutes the usual therapy. Secondary infection is rare.

CORNEOSCLERAL LACERATIONS (RUPTURED GLOBE)

A penetrating or perforating injury represents a full-thickness scleral or corneal laceration. This is a serious ocular emergency requiring immediate medical attention. The history typically describes a sharp object striking the lid or eyeball. The globe can also be ruptured through severe blunt impact. Taking a careful history is essential to identify the risk for infection or a foreign body and the likelihood that the latter can be detected by CT or magnetic resonance imaging (MRI).

Clinical findings depend on entry site. Frequently the lids and conjunctiva are markedly swollen with severe subconjunctival hemorrhage. In some cases, the eye may look remarkably normal until further exploration reveals the damage (Fig. 573-2). The eye attempts to naturally seal a rupture by having the uveal tract (choroid for lacerations of the sclera, iris for lacerations of the cornea) plug the wound. When the cornea is lacerated, the anterior chamber may be shallow with a distorted pupil (Fig. 573-3A). The peak of the pupil will point in the direction of the rupture as the iris flows into the wound (Fig. 573-3B). There may be accompanying hyphema, conjunctival laceration, or subconjunctival hemorrhage. Any black or brown tissue on the sclera after trauma should be presumed to be choroid emerging through a scleral laceration until proven otherwise (Fig. 573-4). If the patient has 360 degrees of subconjunctival hemorrhage or chemosis after trauma, it is impossible to rule out a scleral wound because the sclera is obscured from view. In such cases, urgent ophthalmology consultation is indicated regardless of the quality of the visual acuity. Vision may be surprisingly good even when the sclera has been ruptured.

Once the diagnosis of penetrating ocular injury is suspected, further examination should be delayed and no drops instilled until an ophthalmologist can proceed. As Valsalva maneuvers can cause further extrusion of the globe contents, the child should be kept calm. The eye should be protected with a shield (not patched), and the patient’s condition and need for care around the face and eye should be communicated to other personnel who may be performing ancillary tests such as CT scans. All oral intake should be avoided in preparation for probable surgical repair. Although intravenous antibiotics are usually indicated, placement of intravenous access may be delayed until the child is in the operating room to avoid further struggling and Valsalva maneuvers.

Sympathetic ophthalmia, although a rare condition with an incidence of less than 0.2%, is a feared late complication of severe monocular trauma in which there is an immunologically mediated attack on the unaffected eye. Any severely damaged eye with little or no visual potential should be considered for enucleation or evisceration within the first 7 to 10 days after injury to prevent the development of sympathetic ophthalmia in the contralateral eye.

INTRAOCULAR FOREIGN BODY

The possibility of an intraocular foreign body must be considered with any penetrating injury of the eye. Risk is assessed by history (eg, injury from BB or pellet gun, metal-on-metal contact, dirty implement), examination, and ancillary testing. A child with an unobserved penetrating injury should be considered to have an intraocular foreign body until proven otherwise. An ophthalmologist should be involved with the examination and management as soon as the penetrating injury and foreign body concerns are established. Careful anterior segment and dilated fundus assessment may reveal whether penetration or a foreign body is present. It is possible, however, for small, high-speed foreign bodies to penetrate the eye with minimal findings and cause only transient pain or no pain at all. When there is an obvious perforation site, the remainder of the examination can be performed under anesthesia. A B-scan ultrasound or a CT scan of the orbit and brain may be obtained. MRI scanning is contraindicated in the presence of possible metallic foreign body.

HYPHEMA

Blunt trauma to the globe and surrounding tissues can cause injury that may vary from periorbital ecchymosis to rupture of the globe. Common findings include anterior chamber hemorrhage (hyphema), recession or disinsertion of the iris root (iridodialysis; Fig. 573-5), lens dislocation (ectopia lentis), cataract formation, vitreous hemorrhage, retinal detachment, and traumatic optic neuropathy. What may appear to be a minor blunt injury to the eye may in fact be a very serious intraocular injury. All children with blunt trauma injuries should receive a thorough ophthalmologic evaluation provided there is evidence by history or examination that the globe was actually contacted. As the globe is normally recessed behind the orbital rims, it is somewhat protected from injury.

Hyphema is the condition in which blood is present in the anterior chamber; this results in layering or clotting of the red blood cells. If anterior chamber blood is present as red blood cells in suspension only, visible only by slit lamp examination, the term microhyphema is used. Hemorrhage that completely fills the anterior chamber and obscures any view of the underlying iris and pupil is known as an 8-ball hyphema. Hyphema may also appear as a clot, a layering of blood, or a diffuse dispersion of blood.

Blunt force causes anterior-posterior compression of the globe with simultaneous expansion in the equatorial plane. There is both an increase in the intraocular pressure and a stretching of tissues. A concussion force wave is also transmitted to the posterior pole. Bleeding in the anterior chamber is a result of a ruptured blood vessel(s) in the iris or ciliary body. Common objects causing hyphema in childhood are balls, thrown objects, bungee cords, and fists. Nontraumatic etiologies for hyphema include retinoblastoma, juvenile xanthogranuloma of the iris, and bleeding diathesis from leukemia or other blood dyscrasias.

Patients with hyphema should be referred immediately for ophthalmology evaluation and treatment. The anterior chamber blood may be part of a more extensive injury complex involving the posterior structures of the eye. An important goal of treatment is to prevent vision-threatening complications. Recurrent or secondary hemorrhage occurs in approximately 22% of patients, with a range of 6.5% to 38%. Rebleeding significantly increases the risk of glaucoma, corneal bloodstaining, and peripheral anterior chamber iris to lens scars (synechiae). Hyphema rebleeds usually occur in the first 5 days, usually between the third and fifth days after the initial injury.

Controversy exists over the ideal treatment of hyphema. All treatment should be delivered under the care of an ophthalmologist. Most microhyphemas and small-layered hyphemas can be managed as outpatient cases. Hospitalization may be needed for noncompliant patients/families, patients at high risk for secondary hemorrhage (active toddlers and children with poorly controlled seizures, attention-deficit/hyperactivity disorder, hemoglobinopathies), children with suspected child abuse, and patients with severe associated ocular and orbital trauma. All African American and Mediterranean patients need to be screened for sickle cell trait or disease. Limited activity, with bed rest with bathroom privileges and no school or physical education during the initial days of observation, is also important. The head of the bed should be elevated 30° to 45° to allow the blood to settle to the inferior portion of the anterior chamber. An eye shield should be placed over the involved eye at all times except for medication installation. Administration of 1% atropine drops or other mydriatic cycloplegics is done to prevent the pupil from moving. No aspirin-containing medications or nonsteroidal anti-inflammatory agents should be used. The ophthalmologist may consider using a topical steroid. Consideration for the use of oral antifibrinolytic agents (aminocaproic acid or tranexamic acid) should be limited to hospitalized patients, because they are often associated with nausea and postural hypotension. These agents may need to be combined with antiemetics. Topical aminocaproic acid may prove to be an effective alternative to the oral administration, but this is not currently generally available.

Increased intraocular pressure (glaucoma) may be transient, secondary to mechanical plugging of the trabecular meshwork. If the increased intraocular pressure is persistent, topical and oral antiglaucoma medications are indicated (see Chapter 580). This may be an early or late complication, and continuous monitoring by an ophthalmologist is essential, because glaucoma is often asymptomatic. Patients with hyphema require daily evaluation for visual acuity, rebleed status, intraocular pressure, and overall integrity of the anterior and posterior segments of the eye. Consideration for surgical evacuation of the hyphema should be entertained whenever a total hyphema persists for 4 to 5 days, especially in young children and those with secondary glaucoma.

TRAUMATIC OPTIC NEUROPATHY

Traumatic optic neuropathy may develop following a severe closed head, orbital, or periocular injury. Direct blunt impact to the globe is not required, as forces can be delivered via the facial bones, by fracture of orbital bones, or through stretching/shearing of the optic nerve. Shearing forces within the optic canal can be associated with loss of pial vessels. This may be associated with intrasheath hemorrhage, edema, and direct shockwave trauma to the nerve. Vision loss may be subtle to profound, and the prognosis for recovery is poor. Presenting signs include decreased vision, visual field defects, or a Marcus Gunn pupil. The treatment of traumatic optic neuropathy with high-dose corticosteroid has been controversial. With the current clinical and experimental evidence, there are no data to suggest that high-dose corticosteroids provide any additional vision benefit than observation alone, especially if there is concomitant traumatic brain injury or if traumatic optic neuropathy is older than 8 hours. Surgical decompression of the optic canal may be offered in select cases, especially if the optic neuropathy is progressive.

ORBITAL FRACTURES

Blunt trauma to the eye by an object larger than the opening of the anterior orbit (a fist, elbow, ball) may fracture the orbital rim or wall. Fractures of the rim are caused by direct compression or displacement of the bone. Fractures of the orbital floor and/or medial wall (blowout fractures) are thought to occur from an increase in orbital pressure with a compression force transmitted to the orbital walls, most often resulting in disruption of the weaker floor region. Direct impact on the orbital rim can also transmit a buckling force resulting in the floor/wall fracture.

Orbital fractures are best evaluated by CT scan. The eye and contiguous structures must be evaluated for associated ocular damage. The involvement of other specialties such as neurosurgery and otolaryngology may be needed. Medial rim fractures may be associated with epiphora from injury to the nasolacrimal duct. Blowout fractures, especially those of the floor, may be associated with incarceration of orbital tissue through a trapdoor effect. Children are at increased risk for this type of “trapdoor” fracture due to incomplete calcification of bones. Clinical features are restrictive strabismus with diplopia, enophthalmos, and facial hypoesthesia. The eye may be unable to look in the direction away from the fracture, usually upgaze). The patient may have an oculocardiac reflex (nausea or vomiting and bradycardia) that accompanies entrapment. Overrotation in the direction of the fracture may also occur. If there is associated orbital hemorrhage, the eye may be proptotic.

Orbital roof fractures are more common in early childhood than in older individuals. These result from impact to the brow, often from a fall. This should be suspected with a history of a fall and prominent hematoma of the upper lid. There may be pulsating proptosis if there is a communication with the intracranial space. If there is any suspicion of a roof fracture, urgent neuroimaging by CT scan is indicated.

Blowout fractures resulting in significant restrictive strabismus or severe enophthalmos (2 mm or more) may be considered for surgical repair within the first 2 weeks following injury. Frequently, however, the motility examination will improve spontaneously.

BIRTH INJURIES

The mechanical forces related to the birth process can produce injury to the eyes and eyelids. Injury to these structures occurs in 11% to 59% of all births, with the majority being mild. Birth injuries to the globe and ocular adnexa result from pressure against the bony outlet or the use of instrumentation, especially if labor is prolonged and difficult. Lacerations of the ocular and periocular structures have been reported with sharp obstetrical instrumentation. Amniocentesis needles and monitoring electrodes have been associated with iris cysts, lens injury, retinal scar, hemianopia, gaze palsy, and even blindness. Vision loss, optic atrophy, visual field defects, and cortical blindness have been associated with intracranial bleeds and contusion. Cranial nerve palsies involving IV, VI, and peripheral VII may result from pressure, stretch, or avulsion. Brachial plexus palsy with shoulder dystocia may result in Horner syndrome. Ptosis has been associated with difficult labor or forceps delivery.

The use of forceps during vaginal deliveries can cause deformation of the globe resulting in rupture of the posterior corneal (Descemet) membrane. This is usually monocular and may be associated with ecchymosis of the eyelids, subconjunctival hemorrhage, and variable corneal edema. The corneal edema usually clears within 4 to 6 weeks but may result in high myopia and astigmatism, which can cause severe amblyopia and secondary strabismus.

Retinal hemorrhage is the most common ocular birth injury, with reported frequencies ranging from 2.6% to 50%. Hyphema and vitreous hemorrhages occur rarely. The etiology of retinal hemorrhage is unknown, but several possible mechanisms have been proposed: compression of the head, which causes congestion of the vessels in the neck or cavernous sinus; sudden release of intracranial pressure with birth; asphyxia; increased capillary fragility; impaired coagulability; stress of the first breath; and prematurity. Recently it has been suggested that prostaglandins, which are known to affect vasculature, may have a role. Some studies suggest that retinal hemorrhages are more commonly seen after prolonged labor, nuchal cord deliveries, and in primiparas, but the only clear risk factors are spontaneous vaginal delivery and vacuum-assisted delivery. Retinal hemorrhage may occur after cesarean section but is uncommon. Approximately 50% of newborn retinal hemorrhages are bilateral. Retinal hemorrhage associated with birth usually resolves by 6 weeks of age.

SUGGESTED READINGS

INTRODUCTION

Vision is an essential sensory input from infancy throughout childhood that allows for normal physical, cognitive, educational, and social development and for adult occupational training. Vision is present at birth at approximately a 20/200 level. Visual acuity develops rapidly during the first year, with normal acuity reached by 9 to 12 months of age. Blindness or visual impairment can be assessed in terms of the level of visual function and by scoring functional vision related to quality-of-life achievements. Assessment of visual acuity is the most often used parameter for estimating vision. The assessment of visual acuity in young children is imprecise; therefore, it is necessary to define ranges of visual loss. Also, test results may improve with advancing age and development. Visual function has been categorized into 5 levels of performance, ranging from normal to visually impaired (Table 574-1).

Unsteady eye movements may be evidence of poor vision since early in life. When related to an ocular etiology such as cataracts, retinal abnormalities, or optic nerve defects, pendular nystagmus is often present, which becomes a characteristic jerk nystagmus in lateral gaze. Jerk nystagmus is defined as a slow conjugate drift in one direction followed by a rapid corrective return to fixation. If the vision is very poor, the abnormal eye movements can become more random in many planes and are less sustained. These are sometimes referred to as “wandering eye movements.” Infantile sensory nystagmus may be seen with extreme vision loss in only 1 eye but, in this setting, is characteristically only jerk in type. In addition to infantile sensory nystagmus, other causes of nystagmus must be distinguished and include disturbances of motor origin. It is important to recognize the significance of early-onset nystagmus as a possible sign of early-onset vision loss.

EPIDEMIOLOGY AND CAUSES OF CHILDHOOD BLINDNESS

It has been estimated that there are 1.5 million blind children worldwide and that 90% live in developing countries. Of the estimated 500,000 children who become blind annually, 60% to 80% are estimated to die within 1 to 2 years. The reported prevalence rates of blindness and mortality in children under 5 years are directly related. Reported rates of blindness in England and Scandinavia are 0.25 per 1000 and 0.4 per 1000, respectively, versus 0.65 per 1000 and 0.63 per 1000 in India and Nepal, respectively. The number of “blind years” in children worldwide has been estimated to be half the number of “blind years” caused by cataracts in adults.

The cause of blindness varies greatly between regions, countries, ethnic groups, and level of socioeconomic development. Causes of corneal scarring associated with infections and poor nutrition (eg, vitamin A deficiency) are more frequently seen in underdeveloped countries as compared to the predominance of hereditary disease in closed populations and the greater proportion of retinopathy seen with prematurity, perinatal brain-related abnormalities, and hereditary disease in more affluent populations. Local factors, gender differences, and changing behavior trends can significantly alter the incidence of childhood blindness. It is important to understand that a majority of the causes of childhood blindness are preventable or treatable.

Hereditary Causes of Childhood Blindness

Bilateral congenital cataracts are often hereditary, with autosomal dominant or recessive transmission. Sporadic cases without family history should be considered heritable, and other family members should be screened for evidence of similar cataracts associated with less severe expression. The possibility of related systemic disease should be actively considered, and where indicated, affected children should be carefully examined for evidence of associated anomalies or acquired defects that might suggest an etiology (eg, congenital rubella syndrome).

Hereditary retinal disease causing profound loss of vision should be suspected when the affected eyes appear initially normal in infancy and vision is later lost, although Leber congenital amaurosis, juvenile X-linked retinoschisis, and retinal dysplasia are examples of genetic disorders that can cause blindness at birth. Retinoblastoma neoplasms of the retina may be inherited and heritable. Albinism occurs in all populations and is usually accompanied by an obvious generalized deficiency of pigmentation when compared to family members, although isolated ocular albinism may occur with seemingly normal skin and hair. Childhood glaucoma is responsible for only 5% of childhood blindness but is treatable, so early diagnosis and treatment are of the utmost importance.

Prenatal and Postnatal Causes of Blindness

In the developing nations of Africa and Asia, the most frequent causes of blindness in young children are secondary to infections and nutritional deficiency (vitamin A deficiency). In the United States, cortical visual impairment (CVI), retinopathy of prematurity (ROP), and optic nerve hypoplasia (ONH) are the most prevalent causes. The most common etiologies of CVI are perinatal hypoxia (35%), prematurity (29%), hydrocephalus (19%), and central nervous system structural defects (11%). Most children with CVI have multiple causes. Minimal improvement in vision may occur after recognition in infancy. Potential vision-threatening complications of prenatal infections (eg, rubella, toxoplasmosis), perinatal infections causing ophthalmia neonatorum (eg, gonorrhea, chlamydia), and postnatal infections (eg, herpes keratitis, measles) are tragically seen too frequently in some populations. Many of these infections are preventable or treatable.

Acquired Causes of Blindness in Later Childhood

Most commonly, vision is lost in older children secondary to strabismus or amblyopia. Traumatic ocular injury, including nonaccidental injury (child abuse), also becomes more frequent outside of the neonatal period. In addition to the infectious causes of corneal keratitis with opacification, vision loss may be secondary to meningoencephalitis or to hydrocephalus or brain tumor (eg, craniopharyngioma). Permanent visual loss secondary to unrecognized and untreated glaucoma is infrequent but preventable.

PREVENTION OF BLINDNESS IN CHILDREN

A majority of childhood blindness is preventable. The fact that blindness is so prevalent should be a stimulus for more effective work for future children. Pediatricians must embrace preventive eye care as an essential responsibility. Those involved with prenatal maternal care must continue to work to reduce the incidence of prematurity and the circumstances associated with perinatal hypoxia. Proper nutrition and immunizations must become universal. Attention must be paid to the risks and prevention of perinatal ocular infection, and families must be taught the hazards of alternative ocular treatments when known to be clearly hazardous. With recognition of eye abnormalities, referral for ophthalmologic care should always be encouraged and rewarded. Ideally, tertiary centers should be available to provide high-quality care for eyes at risk due to prematurity and to manage cataracts, glaucoma, and ocular injuries.

Lastly, if a child has 1 eye that has irreparable subnormal vision, then all efforts to protect the unaffected eye must be made, including having the child wear appropriate protective eyewear for sports (eg, goggles, visors, face masks) and full-time glasses with shatterproof polycarbonate lenses, even if the child does not need glasses to improve vision. There is evidence that children with 1 blind eye are more likely to injure their remaining eye. Pediatricians can be instrumental in ensuring that such children are protected.

PROGNOSIS FOR BLIND CHILDREN

In addition to efforts made to reduce blindness in children, care and assistance must also be made for children handicapped by limited vision. This care will require the dedication and work of parents, educators, physicians, and low-vision specialists to allow each child to reach his or her full potential for happiness and for personal development and fulfillment. Worldwide resources available for parents and others to assist with the care of the visually handicapped child should be utilized.

Providing service for visually impaired children should begin with a full ophthalmic evaluation at the time a problem is recognized. If the condition is not amenable to treatment, then supportive measures can be instituted even in infancy. For the completely blind child, parents can be trained in the use of alternate sensory stimuli such as sound and touch. Children who have some vision often function normally up to grade 1 or 2, at which point the visual demands begin separating them from their peers. Low-vision evaluation may then lead to training in the use of a wide range of adaptive technology. If a child can see 20/60 (6/18) or better with both eyes open, they will usually be able to function with normal print size. Particular challenges such as glare, depth perception, loss of contrast, and decreased vision in dim illumination may be characteristic of specific disorders, which require adaptations in the classroom and at home. Computers and low-vision optical and video aids enable many partially sighted, low-vision, and blind children to participate in regular class activities. Educational materials are available through large-print books, books on tape, and Braille books.

Students with visual impairments may need additional help with special equipment and modifications in the regular curriculum to emphasize listening skills, communication, orientation and mobility, vocation/career options, and daily living skills. Students who have low vision or who are legally blind may need help using their residual vision more efficiently and may need help working with special aids and materials. Students who have visual impairment combined with other types of disabilities have a greater need for an interdisciplinary approach and may require greater emphasis on self-care and daily living skills.

Schools for the blind concentrate on teaching students how to deal with issues, such as maximum use of remaining vision, and employ both practical vocational counseling and special technology to provide education. These schools must also make an effort to allow contact with sighted peers and to encourage incorporation of the blind child into the sighted society. Only in the most severe cases are interventions such as white canes, seeing-eye dogs, and Braille needed.

Children are remarkably adaptive. Rather than restrict activity and opportunity based on parental perception, visually impaired children should be allowed to flourish within their own comfort level. Although schools for the blind/visually impaired and low-vision organizations are extremely useful resources, the ultimate goal should be normalization and broadening of opportunity. Pediatricians must engage families to ensure that vision challenges are being addressed.

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INTRODUCTION

Amblyopia is a monocular (or occasionally binocular) reduction of vision due to impaired visual development by the brain. It is sometimes referred to as lazy eye, although this lay term may also be applied to describe strabismus (ie, a wandering eye; see Chapter 576). In addition to subnormal visual acuity, sophisticated testing will also reveal possible deficiency of motion sensitivity, contrast sensitivity, color sensitivity, visual field, and stereoacuity. The functional and anatomic changes in the brain result from disruption of normal visual experience during development. The severity and reversibility of amblyopia relate closely to the cause of the visual disturbance and the child’s age.

Normal visual development requires that both eyes are in good focus, with normal ocular structures and cerebral visual pathways. In addition, both eyes need to be looking at the same thing at the same time. There are 3 main types of amblyopia:

1. Deprivational—caused by physical obstructions to vision such as congenital cataract, corneal opacification, or ptosis occluding the visual axis.

2. Ametropic—caused by asymmetric or, occasionally, binocular refractive error (glasses prescription).

3. Strabismic—caused by misalignment of the visual direction of the 2 eyes.

In deprivational amblyopia, the physical abnormality of the eye or lid itself may cause the vision to be reduced. For example, if an opacity in the lens (cataract) blurs the vision, the brain will prefer the other normal eye and will “ignore” the eye with cataract. Amblyopia will then further impair the visual development in the eye with cataract, causing the vision to be even worse.

The most common form of ametropic amblyopia is anisometropic amblyopia, caused by the 2 eyes having a different focus, such that 1 eye is out of focus when the other is in focus. The defocus can be caused by a difference in the refractive power of the 2 eyes. For example, if both eyes are farsighted—a very common finding in young children that usually does not require glasses—but 1 eye is more farsighted than the other, the brain will prefer to view through the eye with less farsightedness. As a result, when the eye with less farsightedness is focused, the other eye is still not completely focused. The brain will prefer the better-focusing eye, and the remaining eye will become amblyopic.

There is a fundamental difference between strabismic amblyopia and the other 2 forms. Deprivational and ametropic amblyopia result from a lack of a well-focused, formed image on the retina, which leads to reduced vision. In strabismic amblyopia, the retinal images are initially in good focus, but due to the misalignment of the visual axes of the eyes, the brain suppresses the image from 1 eye (as a way to prevent diplopia), resulting in reduced vision from that eye.

Typically, deprivational amblyopia is more severe than strabismic amblyopia, which is usually more severe than amblyopia due to refractive error. Mixed strabismic and anisometropic amblyopia is usually more severe than strabismic amblyopia alone.

Monocular amblyopia causes little if any reduction in the child’s quality of life. But if there is loss of vision in the better (nonamblyopic) eye—for example, due to trauma or other coincidental ocular disease—then a major visual disability may result, as both eyes will have subnormal vision, if not legal blindness. There is an increased risk of losing the better eye, in particular due to trauma, in patients with unilateral amblyopia, and the lifetime risk of vision loss in the better eye is at least 1.2%. It follows that treating amblyopia is likely to be very cost-effective, because the effect of improving vision is felt over the child’s whole life and offers protection should the other eye suffer visual disease.

Binocular amblyopia is much less common than monocular amblyopia. It usually occurs in children who have bilateral high-refractive errors that are not treated with glasses at an early age. This underscores the importance of vision screening by pediatricians at well-child examinations, as a child with uncorrected refractive error might very well appear functionally normal because the visual demands of young childhood do not present a sufficient enough challenge to elicit symptoms. Yet, the child’s brain is not receiving a clear enough image to allow for proper visual development. Later, when the deficit is discovered, it may be too late for glasses to fully correct the problem. If they receive early intervention, some children will show a slow but steady improvement in visual function and typically achieve normal visual acuity within 1 year of being prescribed corrective spectacles.

EPIDEMIOLOGY

Amblyopia affects 2% of the population and is the leading cause of monocular reduced vision in childhood in the world’s wealthier economies. It is more common in children with a family history of conditions such as strabismus, refractive error, and congenital cataract. It is also more common in children with systemic abnormalities such as Down syndrome and premature birth, due to the increased frequencies of strabismus and refractive error associated with these conditions. Bilateral amblyopia has been shown to have a prevalence of 0.5% in one study from Germany. Robaei and coworkers reported that the cause of monocular amblyopia is anisometropia in 34.4%, strabismus in 37.5%, and mixed in 18.8%.

PATHOPHYSIOLOGY

The pathophysiology of amblyopia was, in part, the subject of the Nobel Prize–winning research by Hubel and Wiesel. They studied the primary visual (striate) cortex in 4- to 6-week-old kittens when the eyelid of 1 eye was sutured closed for 3 days or more, from birth. They looked at the size of ocular dominance columns (areas in the striate cortex that carry neuronal input from either the left or the right eye) via the lateral geniculate nucleus in the thalamus. The surgically closed eye had much attenuated ocular dominance columns in the striate cortex, and the open eye had larger than normal columns. This is because the 2 eyes are “in competition” for cerebral neuronal connections; if the image from one is suppressed or out of focus, that eye loses the competition. This period of competition occurs in what is known as the “critical period” of visual development, after which the visual brain loses plasticity. This experimental situation is analogous to that of human infants with a dense monocular cataract. In this instance, good visual results necessitate surgery by 6 weeks of age. After 6 weeks of age, there is a steady and rapid reduction in the chances for the best possible corrected visual acuity due to irreversible organic brain changes in the vision pathways.

In contrast, critical periods for strabismus and anisometropia in humans are longer but not well defined experimentally. Ocular dominance columns in the striate cortex are not anatomically altered in human strabismic or anisometropic amblyopia. Functional magnetic resonance imaging (MRI) studies of brain activity in strabismic and anisometropic amblyopes show that amblyopic eyes have a reduced share of cortical territory than normal eyes. However, many important questions remain to be resolved in this area, particularly the relative impact of amblyopia on the striate versus extrastriate visual processing areas.

DIAGNOSIS

In unilateral amblyopia, the amblyopic eye typically has visual acuity of 2 or more lines worse than the nonamblyopic eye. This finding is a criterion for referral for an ophthalmology assessment. Visual loss in amblyopia ranges from mild to severe, with about 25% of children having visual acuity in the amblyopic eye of worse than 20/100. Amblyopia is detected by measuring visual acuity. Standard visual acuity testing using charts creates a “crowded” stimulus, which accentuates the vision deficit and makes it more likely to be detected. If single letters/figures/numbers are used, the stimulus is no longer crowded and performance will be enhanced. Therefore, pediatricians may miss amblyopia if they use such isolated stimuli. In children who are too young to perform literate or picture tests, the pediatrician must look for an unequal preference of fixation. If such a preference is found, then referral to an ophthalmologist is indicated to ascertain the cause.

TREATMENT

Treatments of unilateral amblyopia consist of optimizing the clarity of the affected eye and occlusion of the visual axis of the unaffected eye to give the brain the opportunity to focus on developing vision in the amblyopic eye. In ametropic amblyopia (unilateral or bilateral), spectacle correction alone may be sufficient. If there is an organic cause of the amblyopia (eg, ptosis, cataract), the abnormality may first need to be corrected (eg, eyelid surgery, cataract removal) before amblyopia treatment can proceed. To the contrary, in strabismic amblyopia, the amblyopia is usually treated first, followed by eye muscle surgery to straighten the eyes; the surgical result will be enhanced if the patient has equal vision in both eyes, thus allowing the brain to have a greater chance of keeping the eyes aligned.

Patching (occlusion) of the sound eye is the mainstay of amblyopia treatment. The patch goes over the periorbital skin of the good eye. If the child is wearing glasses, the patch should go on the skin and not on the glasses as the child will peek over (Fig. 575-1), even though options for occluding 1 spectacle lens are available. In selected cases, in particular for those with a farsighted good eye or mild to moderate amblyopia, optical penalization of the sound eye, typically with atropine eye drops, may also be effective. The drops blur the good eye to a point where the brain now prefers the amblyopic eye. Children are encouraged to engage in visually stimulating near activities during the treatment period to increase the use of the amblyopic eye.

In the last decade, there has been a leap forward in our evidence base for amblyopia treatment, with the advent of multicenter, prospective, randomized clinical trials. The studies have revealed many important findings. Children with monocular ametropic amblyopia, treated with spectacles to correct their refractive error and with patching to correct their amblyopia, have better visual acuity than those treated with spectacles alone or those who are not treated. The results of this study must not be extrapolated to strabismic or deprivational amblyopia. As the mildest form of amblyopia, anisometropic amblyopia is the easiest form to treat, and even teenagers can respond to treatment.

The Pediatric Eye Disease Investigator Group (PEDIG) has published extensively on amblyopia in recent years. They have shown that in the treatment of moderate amblyopia (< 20/100), patching the sound eye for 6 hours or more a day is as effective as using atropine eye drops (1 drop per day, used with sunglasses and a hat in sunlight as needed). Atropine and patching treatments were both well-tolerated and accepted by the child and the family, but overall, atropine received more favorable scores on evaluation by the families. PEDIG compared patching of 2 hours versus 6 hours per day in children under 7 years old with moderate amblyopia caused by strabismus, refractive error, or both. They found no significant difference in outcome, although the improvement with more daily hours of patching was faster. Both groups had their patching combined with 1 hour of near visual activities each day. PEDIG also compared atropine 2 days a week versus daily atropine for moderate amblyopia in children under 7 years old and found no significant difference in outcome. In practice, this means that for moderate amblyopia, in children < 7 years old, treatment with either 2 hours of patching a day or atropine 2 days a week is considered acceptable. PEDIG also reported that full-time patching of the sound eye was as effective as patching for 6 hours a day in patients age 3 to 6 years with severe (20/100 to 20/400) unilateral amblyopia. Both groups had improvement in visual acuity in the amblyopic eye of slightly less than 5 lines of the visual acuity chart.

PEDIG also examined the effectiveness of treating amblyopia in older children, age 7 to 17 years, with baseline visual acuity of 20/40 to 20/400 and found that up to 53% of those age 7 to 12 years and 47% of those age 13 to 17 years (if treatment naïve) could still improve. This study tells us that it is well worth attempting treatment in older children suffering from amblyopia, although compliance may be a challenge. In the past, there had been little confidence in attempting treatment after 7 to 8 years of age. Another question that PEDIG studied was how stable visual acuity improvements are following treatment of amblyopia. They studied 80 patients age 7 to 12 years whose visual acuity had improved by 2 or more lines in the amblyopic eye after treatment with patching or atropine but who had ceased treatment, apart from spectacle wear, for 1 year. Visual acuity in the large majority was stable. However, amblyopia treatment should not be ceased suddenly; up to 25% of patients relapse in the first year after cessation if the therapy is not weaned.

Complications of Amblyopia Treatment

Amblyopia treatment is very safe, provided it is well-supervised. It is possible to produce “occlusion amblyopia” (sometimes referred to as reverse amblyopia), in which the sound eye becomes amblyopic, especially if treatment of the sound eye is not stopped or tapered when the originally amblyopic eye achieves visual acuity equal to the sound eye. This can be avoided by careful follow-up of treated children. Now that they have been shown to be equivalent in efficacy to more intensive regimes, less intensive patching regimes for moderate amblyopia are much less likely to produce this complication than, for example, full-time occlusion of the sound eye. Occlusion amblyopia is particularly uncommon in deprivational amblyopia. For example, children with unilateral congenital cataracts may undergo years of nearly full-time patching without apparent harm to the eye without cataract. But careful follow-up is still advised.

Intractable diplopia is an extremely rare possibility when patching children older than age 7 years. The risk is probably in the order of 1:10,000 or less.

More innocuous complications include contact dermatitis of the periorbital skin due to the patch (Fig. 575-2). This may often be handled by a short course without the patch with or without topical steroids. Switching the brand of patch may also be helpful. If the child is developing abrasions of the periocular skin from removing the patch, parents may place a permanent piece of micropore paper over the affected area and continue patching, with the patch going on and coming off the tape rather than the skin. The micropore tape will spontaneously fall off when the skin underneath is healed. Systemic reaction to atropine eye drops may occur. In such cases, and in children under 1 year old, we recommend atropine 0.5% instead of the more typical 1% solution.

Perhaps the most common problem with patching is noncompliance. Understandably, children will react adversely when asked to view the world with their blurry eye. Infants may fall asleep when the patch is applied, and older children will go to extraordinary lengths to either pull the patch off or resist in other ways. Children may be given the choice of the sting of the atropine or the occlusion of the patch. Other “tricks” are available such as preparations to increase patch adhesiveness, occlusive dressings over the patch, or mitts over the hands. Perhaps most importantly, parents need to use positive reinforcement techniques and have the support of their physicians and similarly affected families. Much information on patching can be found at the website of the Pediatric Glaucoma and Cataract Family Association (PGCFA). It has often been recognized by pediatric ophthalmologists and parents that amblyopia is one of the most difficult eye disorders of childhood to treat because of the compliance issues.

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INTRODUCTION

Strabismus is the term used to describe any ocular misalignment. The term originates from the Greek strabismus, meaning to “look askance” or the “evil eye.” Ocular misalignment that is constantly present and not controlled by fusional mechanisms is termed a tropia. A phoria is defined as a latent deviation that is controlled by fusional mechanisms and only presents when 1 eye is blocked or covered. An intermittent tropia is a deviation that may sometimes be latent and controlled by fusional mechanisms (ie, a phoria) but may at other times be spontaneously manifest, often with illness or fatigue. Most children with strabismus develop a deviation that manifests mostly in 1 eye (the nondominant eye). Some strabismic children are able to switch fixation, using 1 eye at times and the other eye at other times, so that the strabismus will appear to shift from 1 eye to the other. This is termed alternating strabismus. In some children, strabismus develops as a result of poor vision in 1 eye and is termed sensory strabismus. Strabismus may also be the presenting sign of a life-threatening disease (eg, brain tumors with cranial nerve palsy) or vision-threatening conditions such as retinoblastoma or cataract.

Strabismus affects between 1% and 4% of children. The 2 most common types of strabismus are esotropia (cross-eyes, convergent squint, inwardly turned eyes) and exotropia (wall-eyes, divergent squint, outwardly turned eyes). Strabismus has been shown to occur in families and is noted more frequently among children who have other neurologic or medical conditions, including those affected by prematurity, low birth weight, cerebral palsy, craniofacial abnormalities, Down syndrome, other genetic disorders, and intrauterine infection or drug exposure.

Amblyopia is a monocular (or occasionally binocular) reduction of vision due to impaired visual development by the brain. It develops in as many as 50% of children with strabismus. Early diagnosis and treatment of strabismus are therefore crucial to developing optimal, binocular visual function. Brief periods of intermittent esotropia or exotropia may be commonly observed during the first 2 to 3 months of life. This does not require referral to an ophthalmologist. However, any ocular misalignment after 3 months of age should be referred to an ophthalmologist for further evaluation. Likewise, any large or constant deviation should never be considered normal.

In addition to defining strabismus by the direction of the misalignment, it can also be categorized by the consistency of the amount of misalignment in different positions of gaze. A comitant strabismus is one in which the ocular misalignment is the same magnitude (measured by the ophthalmologist in units called prism diopters) in primary (straight-ahead gaze), left, right, up, and down gaze. All of the esotropias and exotropias discussed below are comitant. When 1 or more muscles are paretic or restricted, the amount of strabismus will differ depending on the position of gaze. This is called an incomitant strabismus. Although nearly every paretic vertical strabismus (most commonly a superior oblique [cranial nerve IV] palsy) starts out incomitant (different in different gazes), it often becomes comitant over time. When strabismus is incomitant, the patient may adopt an anomalous head position to put the eyes in a position of gaze where they are most aligned while looking straight ahead. If patching of 1 eye eliminates the anomalous head position, an ocular cause is likely responsible, and referral to an ophthalmologist is indicated.

There are many potential benefits to correcting strabismus. Strabismus surgery is reconstructive rather than cosmetic. Restoration or development of binocular vision can improve fusion, stereoacuity, and binocular visual field and can restore normal visual function in both eyes. This can lead to long-term stability of ocular alignment and help to reduce the number of eye surgeries required throughout a patient’s lifetime. A normal ocular alignment also enhances social interaction and eye contact, while uncorrected strabismus can adversely affect employability.

DETECTION OF STRABISMUS

The pediatrician’s main tool in recognizing the presence of strabismus is the corneal light reflex (Hirschberg test). In normal individuals, a light shone directly or indirectly into the eyes will appear as a white reflex located symmetrically in each pupil. If the eyes are misaligned, then the reflex appears at a different position relative to the pupil in the deviated eye. In esotropia (Fig. 576-1), the reflex appears more lateral in the pupil compared to the straight eye, which is fixating on the light or examiner. In exotropia (see below), the light reflex appears more medial relative to the pupil in the deviated eye. In hyper-/hypotropia, the light reflex is displaced vertically (see below).

ESOTROPIA

Primary Infantile Esotropia

Primary infantile esotropia develops in the first few weeks to months of life, most often prior to 6 months of age. Previously, this condition had been incorrectly termed congenital esotropia. There is often a family history of strabismus, with esotropia observed in as many as 10% to 20% of first-degree relatives. Classic infantile esotropia is constant and involves a large amount of misalignment, often 20 to 30 degrees (40–60 prism diopters) at both distance and near viewing (see Fig. 576-1). Infantile esotropia rarely can resolve spontaneously over time, with the magnitude of deviation being inversely proportional to the probability of resolution. Multiple studies have confirmed that a constant large esotropia that is still present at age 2 to 4 months is unlikely to resolve without treatment, and the angle of strabismus may increase with continued observation.

Normal amounts of farsightedness are present in most of these patients. Glasses are therefore not generally required or helpful, as the esotropia is unrelated to the refractive error. Significant nearsighted or astigmatic refractive error, if present, may require correction, not to improve the alignment but to maximize vision. Managing primary infantile esotropia generally involves eye muscle surgery, which is successful approximately 80% of the time after a single operation. Surgical treatment of infantile esotropia generally involves recession (weakening) of the medial rectus muscles on both eyes. Most clinical experience suggests that very useful, sometimes near-normal sensory and oculomotor functions can be developed or restored if successful ocular alignment is achieved within the first 2 years of life. The optimum timing for eye muscle surgery for primary infantile esotropia is the subject of much research, with some suggesting intervention as young as 6 months of age in an effort to maximize binocular visual potential. Even surgery as early as 13 weeks has been advocated by some ophthalmologists. Botulinum toxin injection into the medial rectus has been investigated as an alternative to traditional surgery. While some authors have noted success with smaller deviations, the efficacy when compared to incisional surgery has not always been convincing.

Careful longitudinal follow-up of these patients is necessary, since an accommodative esotropia (see below) requiring glasses can develop at a later date. Even with successful surgical ocular realignment, patients with infantile esotropia are more likely to exhibit latent nystagmus, vertical misalignment, and monocular smooth pursuit abnormalities. These features may persist throughout the patient’s life.

Accommodative Esotropia

When humans focus on near objects, the ciliary muscle of the eye contracts, resulting in relaxation of the lens (a process called accommodation), and the eyes converge. Children have particularly large abilities to accommodate. This ability is lost in later adulthood, thus the reason for needing reading glasses or bifocals. If a child is farsighted, they need to accommodate even more than usual to focus, and they are able to do so without any sense of stress or discomfort. In fact, most children are farsighted in the first decade of life, and very few need glasses. But in some children, this excess accommodative need results in overconvergence of the eyes, called accommodative esotropia.

Children with accommodative esotropia generally present between the ages of 18 and 48 months of age, with an average age of onset of 2.5 years. The esotropia is often intermittent in the beginning and becomes constant without intervention. The amount of esotropia is generally less than is present in patients with primary infantile esotropia and may be more prominent at near fixation. These children have larger than average amounts of hyperopia, averaging about +4 diopters, with some patients exhibiting as much as +8 to 10 diopters. Over 30% of children with +4 diopters or more of hyperopia will develop esotropia by 3 years of age. Amblyopia may also develop, even bilaterally, in children whose hyperopia is excessively high. Some experts contend that children with accommodative esotropia more frequently have amblyopia at presentation than children with infantile esotropia.

Managing accommodative esotropia usually involves spectacle correction for the farsightedness to eliminate the need to accommodate and overconverge. Bifocals may be required if there is excessive accommodative convergence at near fixation. With the glasses on, the patient has straight eyes. When the glasses are removed, the patient again starts to accommodate in order to see clearly and the eyes are esotropic (Fig. 576-2). The child may actually see as clearly without the glasses as with them, but the glasses are there to keep the eyes straight.

A second form of accommodative esotropia does not involve farsightedness. Children with this subtype of esotropia often have straight eyes, or nearly so, when looking at an object in the distance, but their eyes cross excessively only when fixating on near objects. This is due to an abnormal relationship between accommodation and convergence. These children are most often treated with reading glasses (if correction is needed only for near work) or bifocals (if they also need correction to see clearly at a distance, such as with astigmatism).

A miotic agent such as phospholine iodide, a cholinesterase inhibitor, is sometimes effective in realigning the eyes of patients with accommodative esotropia where compliance with wearing glasses is poor, but potential ocular and systemic side effects of this medication limit its long-term usage.

It is normal for children to demonstrate increasing amounts of hyperopia until 6 to 8 years of age, when the amount of hyperopia naturally begins to decrease in most children. In patients with accommodative esotropia, a gradual reduction (“weaning”) of the spectacle strength may be possible over time, while maintaining good vision and alignment. If glasses are worn faithfully and good fusional patterns are established, many patients with accommodative esotropia can be weaned from their glasses by the time they are teenagers. The same is true for bifocals. When beneficial, bifocal correction can often be weakened after 4 to 7 years of age and even eventually eliminated in over half of cases, usually by the midteens. A few eye surgeons recommend eye muscle surgery for children who cannot be weaned out of bifocals by 15 to 16 years of age. This allows the patient to discontinue bifocal wear and simply wear single-vision glasses or contact lenses.

Some patients will always need glasses (or contact lenses) to keep their eyes straight. Significant delay, as little as 3 to 4 months, in initiating spectacle treatment following the onset of accommodative esotropia increases the possibility that a portion of the esotropia will not resolve with spectacle correction alone. This mixed form of strabismus (partially accommodative esotropia) often requires surgery for the nonaccommodative component.

Basic Acquired Esotropia

Esotropia that develops after infancy and is not accommodative is termed basic acquired esotropia. Organic pathologies, often in the retina or vitreous of the eye (eg, traumatic injury, cataract, Toxoplasma infection), have been diagnosed in a significant percentage of these patients, emphasizing the importance of an ophthalmologist performing a complete eye examination (with pupil dilation) in any patient presenting with strabismus. Underlying central nervous system lesions in otherwise healthy children must also be considered and ruled out by neuroimaging or pediatric neurologic consultation if no ocular pathology is found. Underlying refractive error or amblyopia should also be treated in an appropriate manner.

After ruling out other specific ocular or neurologic pathology, management of acquired esotropia generally requires strabismus surgery. This usually involves bilateral medical rectus recession (weakening) or unilateral surgery with medial rectus recession and lateral rectus resection (strengthening).

Pseudoesotropia

The infant with pseudoesotropia often has a wide, flat nasal bridge with prominent epicanthal folds. The child may appear esotropic even when the eyes are straight, because there is less white sclera visible medially compared to laterally, especially if the child is looking slightly to 1 side or looking up close. This optical illusion causes the child to appear cross-eyed (Fig. 576-3). The Hirschberg light reflex test is normal. While no treatment is necessary for pseudoesotropia, as this appearance will disappear spontaneously as the infant grows older, these children should be reevaluated every 6 to 12 months, since some of these patients may incidentally develop accommodative or acquired esotropia at a later age.

EXODEVIATIONS

Intermittent Exotropia

Intermittent exotropia is the most common exodeviation. The onset of intermittent exotropia usually occurs before 5 years of age, but it may go undiagnosed until much later, even into adulthood. Fusional mechanisms (the natural neural drive to use both eyes together and simultaneously) are present to intermittently control the exodeviation. Initially the eyes deviate only in times of fatigue, visual inattention, or illness, when these mechanisms are reduced. Most patients with intermittent exotropia have normal visual acuity. Intermittent diplopia may rarely be a complaint. Children with intermittent exotropia will often squint or close 1 eye in bright sunlight for reasons that are not well understood. The deviation is generally larger for distance viewing and initially is often not present or greatly reduced with near fixation. The natural history of untreated intermittent exotropia is unclear. Some reports suggest that the exotropia will remain stable or will improve, while most experienced clinicians have found that the majority of patients will deteriorate with long-term follow-up. If the exotropia becomes constant, binocular vision and stereopsis will deteriorate or be lost.

The management of intermittent exotropia can involve both nonsurgical and surgical modalities. Corrective spectacles for any clinically significant refractive error, especially myopia or myopic astigmatism, can improve the fusional control of intermittent exotropia, presumably based on improved vision allowing both eyes to be used together more efficiently. Adjusting the glasses prescription to stimulate accommodative convergence can improve control of the strabismus in patients with intermittent exotropia. Part-time patching of the dominant (nondeviating) eye 4 to 6 hours per day, or alternate patching when no obvious dominant eye is detected, can also be very effective. Patching is rarely curative, and fusional control often deteriorates when patching is discontinued. Intermittent exotropia is one of the few strabismus conditions that may actually benefit from active “vision therapy” or orthoptic treatment, particularly when the exotropia is more prominent at near viewing (convergence insufficiency; see below).

Extraocular muscle surgery is generally considered when an exodeviation occurs frequently or when the amount of deviation is large enough to result in reduced binocularity or poor appearance and has not responded to more conservative management with part-time patching, spectacles, or eye exercises. Timing of strabismus surgery in patients with intermittent exotropia is also controversial. Surgical realignment before 7 years of age, before the duration of exodeviation has reached 5 years, or while the deviation is still intermittent appears to increase the probability of success.

Constant Exotropia

Onset of constant exotropia during early infancy is very unusual and should raise the question of other ocular or central nervous system abnormalities that may require further investigation. There is an increased incidence of constant exotropia in children with perinatal or neurologic risk factors, such as prematurity, genetic disorders, and intrauterine drug exposure. More commonly, constant exotropia is diagnosed in older patients (Fig. 576-4) who have a history consistent with a decompensated intermittent exotropia or with a sensory exotropia caused by any ocular condition that reduces the visual acuity in 1 eye. While infants and young children who lose vision in 1 eye are equally likely to drift in (sensory esotropia) or out (sensory exotropia), older children and adults are more likely to develop exotropia.

Managing constant exotropia with the nonsurgical modalities described in the “Intermittent Exotropia” section is generally unsuccessful and therefore not initiated. Surgical treatment is generally required and usually involves bilateral lateral rectus muscle recessions or a lateral rectus recession and medial rectus resection on the nondominant eye. Patients and their families must be warned that postoperative diplopia immediately after surgery is common in these patients but generally resolves spontaneously or with orthoptic exercises.

Convergence Insufficiency

Patients with convergence insufficiency generally complain of “eye strain,” blurred near vision, or reading problems (asthenopia). These patients often have an exophoria at near and develop intermittent exotropia with prolonged or strong near effort. Patients with convergence insufficiency are good candidates for orthoptic therapy. “Pencil push-ups” (holding a pencil out at arm’s length, the patient focuses on the writing on the pencil and then slowly brings the pencil to near viewing while keeping the pencil in focus) and other near-point exercises are generally employed. Glasses with prisms in the lenses can also be beneficial to stimulate fusional convergence. In addition, computer-based orthoptic exercises are available commercially at a nominal cost. Eye muscle surgery may be required if nonsurgical treatment is ineffective or if compliance is poor.

Pseudoexotropia

In patients with pseudoexotropia, the eyes appear to be turned outward when they are actually straight. It occurs in association with widely spaced eyes or retinal variations, especially following retinopathy of prematurity. The Hirschberg corneal light reflex test will be normal. Children with pseudoexotropia should still be examined periodically during childhood, since true exotropia may develop.

VERTICAL STRABISMUS

Dissociated Vertical Deviation

Dissociated vertical deviation (DVD) is a disorder seen most frequently in patients with infantile esotropia or exotropia. The etiology is unknown. With inattention or occlusion, each eye may slowly drift upward and outward (Fig. 576-5). Initially, the hyperdeviation is latent but may become constant and continuously visible over time, resulting in the need for surgical treatment.

Noncomitant Vertical Deviations

Overaction of the oblique muscles, either inferior oblique or superior oblique muscles, generally results in vertical strabismus that is variable and generally greatest in adduction, where the oblique muscles have the greatest action. The affected eye will either be hypertropic (inferior oblique overaction) or hypotropic (superior oblique overaction) in adduction (contralateral gaze). Oblique overactions can also result in horizontal incomitance in up or down gazes, called A-pattern (eyes farther apart in downgaze and closer in upgaze) or V-pattern (eyes farther apart in upgaze and closer in downgaze). Patients may keep their chin up so that their eyes are most aligned when looking straight ahead. Management of oblique muscle overaction, if significant or symptomatic, requires eye muscle surgery.

CRANIAL NERVE PALSIES

Cranial Nerve IV Palsy

The trochlear nerve (cranial nerve IV) innervates the superior oblique muscle. This palsy may be congenital or may result from head trauma or intracranial tumors. The long intracranial course of the nerve makes it uniquely susceptible to injury. The palsy may be unilateral or bilateral. Most commonly, affected patients will have a hypertropia of the involved eye and a head tilt to the opposite side. When the defect is congenital, the spontaneous head tilt can be mistaken for a sternocleidomastoid muscle problem, and the patient may be referred to an orthopedist or physical therapy. If the head tilt improves when 1 eye is covered, the nature of the problem is ocular, most likely a superior oblique palsy. Children with congenital superior oblique palsy also often develop a characteristic facial asymmetry, with mild hemifacial microsomia on the dependent (lower) side of the face and a curving of the nose toward the affected side, which can be diagnostic.

Patients with small vertical deviations can sometimes be managed with prisms in the lenses of their spectacles. This method is most applicable when patients already require spectacles to see clearly. Most cases of acquired cranial nerve IV palsy should be observed for spontaneous improvement for at least 6 months. At that time, if the patient is symptomatic and the deviation is not controlled with a head tilt or prisms, eye muscle surgery is indicated.

Cranial Nerve VI Palsy

Cranial nerve VI (abducens nerve) innervates the lateral rectus muscle, which abducts the eye. Transient, benign, unilateral abducens palsy is rarely seen in the newborn period and resolves over 2 to 3 months. Spontaneous abducens palsy (often called benign postviral VI palsy) may also occur in childhood, often after viral illness. Acquired abducens palsy is most commonly seen after closed head injury or in association with increased intracranial pressure. A significant number of cases are associated with intracranial lesions and may have associated neurologic manifestations. Abducens palsy is characterized by esotropia in primary gaze that increases in ipsilateral side gaze. Limited abduction, diplopia, and either a head turn toward the side of the paresis or monocular eye-closing are also often seen.

When there is not a clear history of trauma, a careful history should be taken to define previous infections or immunizations. Neuroimaging should be considered whenever other neurologic signs or symptoms are present. Depending on the child’s age, patching may be required in younger children to prevent the development of amblyopia. Fresnel press-on prisms can be applied to spectacles to eliminate diplopia in primary position, improve anomalous head postures, and prevent amblyopia. Spontaneous resolution can be expected in the majority of acquired idiopathic, postviral, and posttraumatic VI palsies. Therefore, observation for at least 6 months prior to surgical intervention is generally recommended. Some surgeons may inject botulinum toxin into the ipsilateral medial rectus muscle to reduce symptomatic diplopia and prevent contracture of the medical rectus while awaiting spontaneous recovery of abduction. Surgery is indicated when spontaneous resolution does not take place and after exclusion or treatment of intracranial pathology.

Duane retraction syndrome (DRS) can mimic a cranial VI palsy but has a much more benign implication. It has been described with a spectrum of motility abnormalities, including limited abduction or adduction or both abduction and adduction, resulting in esotropia, exotropia, or orthotropia in primary gaze. The common denominator is globe retraction in attempted adduction. DRS type 1, with deficient abduction, is the most common form and most confused with cranial VI palsy (Fig. 576-6). Careful observation for globe retraction on adduction, best viewed from the side of the patient, and narrowing of the palpebral fissure (Fig. 576-6) can save the patient a neurologic workup for cranial nerve VI palsy. The motility problem is congenital (but often not noticed for months or years due to compensation by the child by turning the head to look to the affected side), usually unilateral (but may be bilateral in up to 10% of cases), more frequently seen in girls, most often present on the left side, and usually sporadic.

Most DRS patients have some position of gaze in which the eyes are aligned so that the majority develop very good binocular vision and avoid amblyopia. While most DRS patients have the ocular motility disturbance as an isolated finding, DRS has been associated with systemic syndromes such as Goldenhar syndrome. The etiology of the motility disorder in most patients appears to be a congenital absence of the cranial nerve VI nucleus in the brain stem. There is also anomalous innervation of the affected lateral rectus muscle by a branch of cranial nerve III, which results in co-contraction of the medial and lateral rectus muscles on adduction, producing the globe retraction. Surgery is indicated in DRS patients who have significant strabismus in primary position and for those who assume a significant abnormal head position, most commonly a face turn.

Cranial Nerve III Palsy

Paresis of cranial nerve III (oculomotor nerve) is fortunately infrequent in childhood, but when present, it can be devastating to the visual system and visual development. This is because 4 of the 6 extraocular muscles, the levator palpebrae, and muscles of accommodation are all innervated by this nerve. Nearly half of pediatric cranial nerve III palsies are congenital. Acquired oculomotor palsies in children can result from trauma, serious infection, and, less commonly, tumor. Characteristics of this palsy include unilateral ptosis, anisocoria (unequal pupils), and strabismus. The child’s affected eye is “down and out,” exotropic and hypotropic, from unopposed action of the superior oblique muscle and lateral rectus muscle.

Management of children with oculomotor nerve palsy is very difficult. Amblyopia is usually present and difficult to treat. Patients who do not recover from the palsy after 6 to 12 months may be considered for eye muscle surgery. In most cases of severe cranial III palsy, the best achievable outcome is alignment of the eyes and possibly single binocular vision in primary position. Ptosis surgery is also often required.

OTHER DISORDERS

Brown (Superior Oblique Tendon Sheath) Syndrome

Brown syndrome is the limited elevation of the affected eye in adduction. This syndrome most commonly presents as a congenital form but can occur secondary to trauma or inflammatory conditions in the area of the trochlea. Restriction of free passage of the superior oblique tendon through the trochlea is common to all forms of Brown syndrome. Observation alone without intervention remains the most common management for all presentations of Brown syndrome since the strabismus (hypotropia) is usually present only in upgaze in the adducted position. Intervention is indicated when there is a significant hypotropia in primary position or when the child has to assume an abnormal chin-up or face-turn head position to maintain binocular vision. For posttraumatic and inflammatory-associated Brown syndrome, oral anti-inflammatory agents or local steroid injection can help select patients improve.

Monocular Elevation Deficiency Syndrome

Monocular elevation deficiency syndrome (formerly “double elevator palsy”) is a congenital condition associated with hypotropia and sometimes ipsilateral ptosis associated with an inability to look upward with the affected eye. The etiology of this condition is unclear but must be differentiated from a central nervous system cause involving the superior colliculus such as increased intracranial pressure or tumor. Surgical intervention is indicated if a significant hypotropia exists in primary position or if the child assumes a large chin-up posture in order to fuse.

Congenital Cranial Dysinnervation Disorders (CCDD)

This family of disorders results in strabismus, almost always incomitant, due to congenital abnormalities of muscle innervation. Duane syndrome and Brown syndrome (see above) may be included. The prototype disorder is congenital fibrosis of the extraocular muscles (CFEOM), a rare genetic entity characterized by secondary fibrosis of individual extraocular muscles, usually bilaterally, with various amounts of restriction of eye movement into the opposite field of gaze. The spectrum ranges from isolated fibrosis of a single muscle to bilateral involvement of all the extraocular muscles. Patients have reduced eye movements and anomalous head positions. Surgical management is very difficult and requires the operative release of the restricted muscles. Restoration of ocular motility is not possible. An optimal result can merely mean straight eyes with little movement in primary position.

Other disorders classified as CCDD include horizontal gaze palsy with progressive scoliosis (HGPPS) and Möbius syndrome.

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INTRODUCTION

All forms of child abuse may have ocular manifestations. It has been estimated that 4% to 6% of cases of child abuse present first to the ophthalmologist. (For a general discussion of child maltreatment, including abuse, see Chapter 36.)

PHYSICAL ABUSE

Any injury to the eye can be the result of child abuse. Some ocular findings are highly suggestive, if not diagnostic, for trauma (Table 577-1), but this does not inform the clinician as to the etiology of the trauma: abusive versus accidental. Appropriate attention to history, laboratory values, and diagnostic testing and the careful search for other signs of abusive injury are necessary to differentiate abusive from accidental injury.

Perhaps the most common reason that an ophthalmologist is involved in child abuse cases is to search for retinal hemorrhage when there is a concern that an infant has been injured through repetitive acceleration-deceleration mechanisms. Intraocular hemorrhages are the most common ocular finding in shaken baby syndrome (SBS), occurring in approximately 85% of victims. Less common findings include traumatic retinoschisis (splitting of the retinal layers), perimacular folds, vitreous hemorrhage, retinal detachment, or total disruption of the ocular contents. In contrast, nonabusive blunt head impact causes retinal hemorrhage in less than 3% of cases unless the injury is from a severe motor vehicle accident, when the prevalence may rise to 17%. Occipital impact or children with accidental epidural hemorrhage may also result in a higher incidence of retinal hemorrhages. Numerous medical conditions can result in retinal hemorrhage. In SBS, two-thirds of the hemorrhagic retinopathies are severe, with hemorrhages in front of (preretinal), within (intraretinal), and under (subretinal) the retina (Fig. 577-1). The hemorrhages may be too numerous to count and extend throughout the retina to its edge (ora serrata).

Hemorrhage extending to the ora is statistically correlated with abuse. The hemorrhages may be unilateral or asymmetric between the 2 eyes. With the exception of fatal crush injury to the head, severe fatal motor vehicle accidents characterized by repetitive acceleration-deceleration (severe rollover), ruptured aneurysm, birth, leukemia, or purulent meningitis, this extensive pattern is usually not seen with other conditions. Of course, these conditions are readily distinguished by history, imaging, or laboratory testing. Although some victims of abusive head injury will have no retinal hemorrhages and some will have a sparse number of hemorrhages confined only to the posterior aspects of the retina (the posterior pole; Fig. 577-2), the latter should still be considered a nonspecific but possible indicator of abuse. One should always consider the number, type, and pattern of hemorrhages when formulating a differential diagnosis. One cannot precisely determine time of injury on the basis of retinal hemorrhage, although some patterns may be helpful.

Most researchers and clinicians now believe that the etiology of retinal hemorrhages is secondary to traction on the retina applied by the firmly attached vitreous gel as it is submitted to acceleration-deceleration forces. Some authors have theorized that hemorrhage may be the result of decreased retinal venous outflow due to increased intracranial pressure or increased intrathoracic pressure presumably from the perpetrator squeezing the child’s chest, at times hard enough to cause rib fractures, yet retinal venous obstruction (ie, central retinal vein occlusion) is rarely observed. Increased intracranial pressure may cause a small number of retinal hemorrhages on or around the optic nerve, particularly when papilledema is present, but a severe hemorrhagic retinopathy is not observed. Papilledema is seen in less than 8% of SBS victims.

Retinoschisis and perimacular retinal folds, which may be isolated or occur in combination, are a distinctive but not pathognomonic finding in SBS. A fold may encompass just the macula or surround the entire posterior pole. These findings have never been reported in nonabused children less than 5 years old, with the exception of similar, although not identical, findings in victims of fatal head crush injury, severe fatal motor vehicle accident, and a 35-foot fall onto concrete. Sub–internal limiting membrane blood seen with leukemia or ruptured aneurysm may also show similarities to these lesions seen in child abuse.

Victims of SBS may suffer long-term visual impairment. The most common causes are cortical visual impairment from brain injury and optic atrophy. The latter appears to be due to direct injury to the optic nerve or its blood supply in the orbit, as the globe may also experience repetitive acceleration-deceleration. Postmortem removal of the orbital tissues along with the globe is recommended to uncover orbital hemorrhage and injury that may provide specific evidence of abuse.

Ophthalmology consultation is essential in a child less than 5 years of age who is felt to be a possible victim of abusive head injury. Only the ophthalmologist can view the entire retina, as this requires pharmacologic dilation of the pupils and indirect ophthalmoscopy. Although many pediatricians show considerable skill in identifying the presence or absence of hemorrhage, they are less able to detail the types of hemorrhage, because direct ophthalmoscopy does not visualize the edges of the retina. Ophthalmology consultation is necessary to delineate the type of hemorrhages and to recognize patterns that have possible specificity for abuse.

MEDICAL CHILD ABUSE (MUNCHAUSEN SYNDROME BY PROXY, FACTITIOUS ILLNESS BY PROXY)

The most common ophthalmic manifestations of this form of abuse are subconjunctival hemorrhage due to covert suffocation, or pupillary abnormalities, nystagmus, or other eye movement abnormalities secondary to covert poisoning. Other reported abnormalities include corneal scarring from the covert installation of noxious chemicals, periorbital and orbital cellulitis from covert periocular injections, and papillary abnormalities due to direct installation of pharmaceutical agents. For a more complete description of this syndrome, see Chapter 36.

SEXUAL ABUSE

The presence of sexually transmitted disease in the eye should be considered suspicious for abuse in nonneonatal prepubertal children. Syphilis has many ocular manifestations and is known as “the great imitator” in the eye. This infection is only transmitted sexually. Other infections with ophthalmic manifestations are known to be transmitted both sexually and nonsexually, including human immunodeficiency virus. There is some evidence that gonorrhea and chlamydia, although only transmitted to other orifices by sexual contact, may be nonsexually transmitted to the conjunctiva due to its unique position as an external mucous membrane. Pubic lice may also be transmitted nonsexually. The presence of gonorrhea, chlamydia, or pubic lice should at least prompt consideration of possible covert sexual abuse and result in a full evaluation, including the culturing of other sites, interview by a trained professional experienced in this area, and examination of the genitalia and anus. If this workup is entirely negative, reporting to child protective services may not be indicated.

Herpes simplex and molluscum contagiosum are so frequently transmitted by nonsexual means that such a workup is not indicated. One must also be careful to consider the late presentation of perinatally transmitted infection, in particular chlamydia, which can present even 2 to 4 years after birth. Gonorrhea conjunctivitis in older children may not have the hyperacute purulent presentation commonly seen in neonates. Treatment should still be aggressive, as gonorrhea can result in corneal perforation. For more discussion of sexual abuse, see Chapter 36.

MEDICAL NEGLECT

The failure to follow through with ophthalmic treatment can be the cause of significant visual loss. In particular, when patching therapy has been recommended for treating amblyopia, failure to comply may result in permanent legal blindness. The approach to ophthalmic neglect and noncompliance should be similar to that for any pediatric medical condition. The use of written contracts may be helpful in that child protective services may be more likely to act if a contract signed by the parent has been broken.

EMOTIONAL ABUSE

Perhaps there is a form of abuse in which children are allowed to see things that are inappropriate for their age and development. In one study, children witnessed a frightening amount of violence, including murders and stabbings, while in grade school and high school. Children also witness sexual activity, pornography, drug abuse, and domestic violence. Protecting children from these visual images is an important part of maintaining their psychosocial health.

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INTRODUCTION

For the pediatrician, a child with a red eye can be a significant challenge; the key decision is whether to refer to a pediatric ophthalmologist. The diagnosis is often reasonably clear after a careful history has been obtained. The examination may be challenging without the availability of an accurate visual acuity test for each eye, appropriate diagnostic eye drops, microscopic examination, and the distraction devices that pediatric ophthalmologists often use. Making an incorrect diagnosis in a child with a red eye can result in vision loss, and inappropriate treatment can have vision-threatening side effects. The pediatrician is occasionally tempted to treat a red eye with steroid eye drops, but this should only be prescribed by a physician able to do a complete eye examination and measure intraocular pressure. Therefore, in practice, steroids should not be prescribed by pediatricians or family physicians.

Conjunctivitis is a common problem in childhood. The conjunctiva becomes red and inflamed in response to a wide range of inciting agents, such as infections, allergens, chemicals, smoke, trauma, toxins, and systemic diseases. Red eye is not a common feature of congenital glaucoma or nasolacrimal duct obstruction. This chapter focuses on diagnosis and treatment of injected or red conjunctiva. The differential diagnosis and management of a red eye are outlined in Tables 578-1, 578-2, 578-3, 578-4. These tables do not provide exhaustive lists, but rather present the scope of problems that may lead to a red eye. History taking is more likely to lead to the correct diagnosis if this broad range of possible diagnoses is considered. Figure 578-1 provides a useful guide to evaluating a child with a red eye.

NEONATAL CONJUNCTIVITIS

Conjunctivitis of the newborn (ophthalmia neonatorum) is one of the most common infections in the first month of life. Time of onset is an unreliable predictor of etiology. The primary objective in evaluating a neonate with conjunctivitis is to rule out gonorrhea, as this organism can cause corneal perforation. Neonatal gonococcal conjunctivitis is usually “hyperacute,” with extremely purulent, copious discharge and marked lid swelling. An emergency Gram stain is indicated, along with appropriate culture and sensitivity testing. Treatment may be started on the basis of the Gram stain alone. Some bacteria may be resistant to penicillin; therefore, third-generation cephalosporins, administered systemically, are recommended. Frequent topical lavage with normal saline is important for decreasing bacterial load and cytotoxins, which lead to keratopathy. Parents and contacts should be referred for testing, and the child and others should be screened for other sexually transmitted diseases such as chlamydia. An ophthalmologist should co-manage the child with the pediatrician.

Chlamydia conjunctivitis typically presents 5 to 25 days after birth but may occur earlier or later. It is more common than other causes of conjunctivitis in newborns, with a prevalence of 3 to 4 per 1000 live births. It usually presents unilaterally but often becomes bilateral. It is diagnosed using nonculture tests—enzyme assay, direct fluorescent antibody, and polymerase chain reaction (PCR)—and culture. Discharge may be mild or more prominent. Treatment of the infant, the mother, and the mother’s sexual contacts, usually with erythromycin or azithromycin, is indicated. This should be augmented with topical erythromycin ointment for the child. If this condition is left untreated, pneumonitis may develop in 20% to 40% of affected children in the first 3 months after birth. Although commonly used in the past, prophylaxis against ophthalmia neonatorum with topical silver nitrate solution is now rarely used, as it may cause a chemical conjunctivitis in the first few days after birth. Less toxic forms of prophylaxis are currently used, such as topical povidone-iodine or erythromycin eye ointment (see Chapter 572).

Other causes of neonatal conjunctivitis are less common. Herpes simplex conjunctivitis occurs infrequently in neonates who are exposed to maternal herpes during birth. Herpes keratitis may cause vision-threatening scarring of the cornea. Skin lesions are almost always present, and the child may develop herpetic encephalopathy.

CONTACT LENSES

Contact lens wearers are at an increased risk of microbial keratitis and should be presumed to have this if they present with a red eye, even if the lens has already been removed. They should be referred urgently (within 12 hours) to an ophthalmologist. If possible, the contact lens should be removed. Usually the child (or parents) will be expert at this, but topical anesthetic may make it easier for the patient or the physician to remove the lens. Once removed, fluorescein staining may help to show an obvious area of corneal epithelial defect or ulcer.

In a cooperative child, it may be possible to evert the upper eyelid, allowing inspection of the palpebral conjunctiva for a lost contact lens or enlarged subconjunctival lymphoid tissue (“giant papillae”) that sometimes occurs in contact lens wearers.

FOREIGN BODY

The sensation of a foreign body in the eye is a nonspecific symptom that may be caused by any disturbance of the cornea or conjunctiva. Tiny foreign bodies may be difficult to see and require a magnified view with a slit lamp or direct ophthalmoscope. Fluorescein staining may facilitate detection of a foreign body (see Chapter 571). A foreign body under the upper eyelid will sometimes produce vertical, linear scratches on the cornea that stain with fluorescein. These are a good clue to the etiology of the red eye.

A cooperative child may allow removal of a foreign body with topical anesthesia and a sterile damp cotton swab or forceps, but sometimes removal under general anesthesia and use of a needle are necessary, in which case ophthalmology consultation is indicated.

ABRASIONS

Conjunctival and corneal abrasions are reasonably common and are sometimes caused by a fingernail or other sharp object coming in contact with the eye. A careful and detailed history of any trauma to the eye is essential. Topical anesthetic drops can be used diagnostically; if pain is relieved, the irritation is arising from the ocular surface. Fluorescein staining will identify the abrasion (see Chapter 573).

INFECTIOUS NONNEONATAL CONJUNCTIVITIS

Conjunctivitis can be infectious, allergic, or chemical. Typically, there is a watery or mucous discharge and diffuse injection of the conjunctiva, and there may be associated eyelid edema. The most common infectious cause is viral conjunctivitis, most often due to adenoviruses. There may be an associated upper respiratory tract infection. Viral conjunctivitis is highly contagious and spreads by eye-to-hand contact. Parents are advised to use a separate hand towel for their child and to wash their hands after touching the child’s eye, hands, or secretions. The cornea may be affected, initially with a fine, diffusely spread, punctate epithelial disturbance, followed by subepithelial infiltrates. Both can produce photophobia. It may be appropriate to seek ophthalmology consultation, because photophobia with corneal pathology may require specialized treatment. Steroid eye drops are not indicated, except in the most severe cases, and then only under the care of an ophthalmologist, who must exclude herpes simplex keratitis and monitor for steroid-induced side effects.

Viral conjunctivitis is typically self-limited and can last from a few days to 4 weeks or more. If the course is prolonged, the condition is most likely epidemic keratoconjunctivitis, due to adenovirus serotypes. Viral conjunctivitis often begins with unilateral involvement, becoming bilateral after a few days. There is often a swollen preauricular or submandibular lymph node. Other viruses that can cause conjunctivitis include coxsackieviruses and echoviruses. Primary herpes simplex infection can cause conjunctivitis, and while this is usually accompanied by skin lesions, it can occur without skin involvement. More typically, the first infection involves the skin only and later recurrences involve the eye. Herpes simplex is almost always unilateral. It is characterized by a dendritic corneal lesion, revealed by fluorescein staining. This lesion may not be noted with later recurrences. Ophthalmology consultation is indicated in any child with possible herpetic infection or in any child with a red eye who has a history of herpetic infection.

Bacterial conjunctivitis is typically more purulent than viral conjunctivitis and becomes bilateral within a very short period. It is a common disorder in young children, and typical organisms include Streptococcus pneumoniae, Moraxella, and nontypeable Haemophilus influenzae. In teenagers, it is important to rule out sexually transmitted organisms, such as gonococcus, chlamydia, and herpes simplex, although there is some evidence that the unique external nature of the conjunctival mucous membrane may allow for nonsexual transmission. Cultures may be helpful, but many pathogenic organisms can be found in conjunctival cultures of asymptomatic children. The choice of antibiotic depends on the cause, but often a broad-spectrum drug such as combined trimethoprim sulfate and polymyxin B sulfate ophthalmic solution is used. Outside North America, chloramphenicol is still used commonly. In general, antibiotic drops are used 4 to 6 times daily, or ointment 2 to 4 times daily, for approximately 1 week. The choice between drops and ointment is that of the physician and parent.

Eye drops can be applied while the child is lying or sitting up and having the child look at the ceiling. In children who do not easily allow direct application, drops can be placed in the medial canthus area (at the medial junction of the eyelids) and gravity allows the drops to enter the conjunctival sac. The child can close the eyes as the drops are applied, which reduces anxiety, and is told to expect a “wet feeling” on the lids. The child is then asked to blink, allowing the drops to enter the conjunctival sac. It is worth remembering that the conjunctival sac can accommodate only about one-quarter of an eye drop, so some excess is expected to spill out of the sac.

ALLERGIC CONJUNCTIVITIS

Allergic conjunctivitis is common and typically seasonal, being worse in spring and summer. It is often accompanied by nasal congestion (rhinoconjunctivitis). It is also known as “hay fever” conjunctivitis and represents a type I hypersensitivity response to a seasonal allergen. Onset is subacute, and attacks may be short-lived. A hyperemic reaction of the tarsal and bulbar conjunctiva is accompanied by edema of the conjunctiva and lids and results in profuse lacrimation and itching. The itching is usually far more conspicuous than in infectious conjunctivitis. There may be a scant, stringy mucoid discharge containing a variable number of eosinophils. Histamine and IgE levels in tears are elevated, but this test is rarely used.

The initial approach to management includes educating the parents and child to avoid allergens and cigarette smoke, applying cold compresses, and using pharmacotherapy. There are few data on the effect of allergen avoidance or how much allergen exposure needs to be reduced to help resolve the disorder. It is also unclear whether sufficient allergen reduction can be achieved in the child’s environment to be clinically useful. The effect of avoiding pet allergens is also unclear from currently available evidence.

First-line treatment in allergic conjunctivitis is an H₁ antagonist/mast cell inhibitor combination (olopatadine, azelastine, ketotifen). Topical corticosteroids (used short-term and only under the supervision of an ophthalmologist) may be helpful for acute flare-ups. Reduced daily dosage of longer-acting agents (eg, olopatadine) may improve compliance and effectiveness.

Vernal conjunctivitis represents the severe end of the spectrum of allergic eye disease, typically presenting between ages 3 and 5 years. It is a problem throughout the year but is typically worse in spring and summer. In addition to the symptoms above, there is usually a significant problem with photophobia due to limbal or corneal inflammation. “Shield ulcers” caused by large, upper tarsal conjunctival giant papillae, which are so big they abrade the cornea, may also occur. Another form of vernal conjunctivitis affects the limbus around the corneal edge and presents as fleshy gelatinous elevations. Children with chronic allergic conjunctivitis or abnormalities on upper lid eversion, suggestive of vernal conjunctivitis, should be referred to an ophthalmologist. Severe allergic and vernal conjunctivitis are now treated more often with topical cyclosporine 0.1% drops. When this is not available, some ophthalmologists use tacrolimus 0.03% ointment. It is not licensed for use in the eye but is widely used by ophthalmologists in the eye, as well as on the periocular skin.

OCULOCUTANEOUS ETIOLOGIES

Oculocutaneous disorders that can cause conjunctivitis include Stevens-Johnson syndrome (erythema multiforme major), toxic epidermal necrolysis, and graft-versus-host disease. These all can cause blindness due to corneal scarring. Involvement of an ophthalmologist is essential.

Blepharoconjunctivitis, with or without rosacea, is caused by an inflammation of the eyelid margins secondary to suboptimal flow from the meibomian glands of the eyelids. There are 20 to 25 of these glands in each upper and lower eyelid, lying vertically within the fibrous tarsal plate of the lid and opening onto the eyelid margin posterior to the eyelashes. Suboptimal flow of the glands is associated with thickening and redness of the lid margins, along with crusting and flaking at the base of the lashes. Hordeolum, either external (stye) or internal (chalazion), represents a completely blocked gland. Styes and chalazia are often recurrent and affect more than 1 lid. The conjunctiva can be red because of the associated dry eye caused by the relative lack of lipid in the tear film or because of the poorly understood hypersensitivity reaction thought to occur as a result of staphylococcal toxins released into the tear film by excess lid-margin bacteria.

Treatment mainly consists of eyelash scrubs once or twice daily. Traditionally, baby shampoo was recommended on a washcloth and the lashes gently scrubbed while the lids are closed. This soapy preparation helps to unblock the meibomian gland orifices. A nonsoaped wet cloth is then used to wipe away the suds. Today, many ophthalmologists are prescribing propriety formulations such as SteriLid or LidCare due to concerns that baby shampoo can interfere with the lipid layer of the tear film. In more severe cases, erythromycin ointment can be applied to the lashes immediately after the scrub. This condition is chronic and requires long-term daily treatments, although the use of antibiotics is usually indicated for only 1 to 2 weeks. If the problems of red eye and photophobia persist, referral to an ophthalmologist is advised. Presence of a phlyctenule, an elevated white nodule within the surrounding injected conjunctiva that results from a hypersensitivity reaction to Staphylococcus, also requires ophthalmology consultation. In children with rosacea or severe aggressive blepharoconjunctivitis, systemic treatment with erythromycin (or tetracyclines in older children) may be helpful. Newer evidence has found azithromycin to be superior as it has fewer side effects and can be administered in short courses of only 5 days while remaining equally efficacious.

FOCAL CONJUNCTIVITIS

Focal or sectoral conjunctival injection can be due to a variety of disorders, including episcleritis; scleritis; ingrowing eyelashes (trichiasis); foreign bodies; herpes simplex or varicella (chickenpox) lesions on the conjunctiva; and rarely such conditions as conjunctival nevi, warts (human papillomavirus), or conjunctival telangiectatic blood vessels associated with ataxia telangiectasia (Louis-Barr syndrome).

Older adolescents exposed to significant amounts of ultraviolet light may develop pingueculae of the nasal (and sometimes temporal) conjunctiva. These are elevated areas of conjunctival degeneration from sun damage. They are wedge-shaped, yellow-white in color, and located adjacent to the limbus. When inflamed or dry, they appear as a focal area of conjunctival redness. They are rare in young children.

Episcleritis is a self-limiting disorder, with attacks lasting up to a month and often recurring. There is a circumscribed area of redness deep to the conjunctiva, which can become elevated or nodular. No cause is usually found in children, but some children may have this disorder in combination with autoimmune systemic disease. Scleritis is much more likely associated with underlying collagen vascular disorders or herpes zoster and can have sight-threatening consequences. Like episcleritis, it can present as a localized or a generalized red eye often with a purple hue, but pain is the predominant feature. Referral to an ophthalmologist is indicated if either episcleritis or scleritis is suspected.

UVEITIS

Photophobia and circumlimbal red eye are prominent features of anterior uveitis (iritis; see Chapter 580), except when the iritis is associated with juvenile idiopathic arthritis (JIA) and related disorders, such as enthesitis, or with psoriasis. Children with JIA may be asymptomatic and detected only at screening by an ophthalmologist. In severe disease, red eye along with a distorted pupil due to posterior synechiae (adherence of the iris [pupil] margin to the anterior surface of the lens) may occur, but a lack of symptoms does not exclude the presence of uveitis. Ophthalmology consultation is required.

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THE EYELIDS

The eyelids are an important part of the ocular adnexa. They provide a mechanical barrier against the environment, distribute the tear film, and remove debris from the ocular surface. In the normal eyelid, the margins should be symmetric and parallel to one another. The upper margin should rest 1 to 2 mm below the superior edge of the cornea, and the lower margin should rest at the inferior edge of the cornea. Generally, the lateral canthus is positioned approximately 1 mm higher than the medial canthus, giving a slight upward slant to the palpebral fissure as one moves laterally.

CONGENITAL ANOMALIES OF THE EYELID

Cryptophthalmos, Ablepharon, and Ankyloblepharon

Congenital anomalies of the eyelid are rare and result from improper or absent differentiation during embryogenesis. The most severe congenital eyelid anomaly is cryptophthalmos, the partial or complete absence of ocular adnexal structures including the eyebrow, palpebral fissure, and conjunctiva. In this condition, skin is continuous over the globe and passes from forehead to cheek without interruption. Visual prognosis is poor as the underlying cornea is often malformed and fused with the overlying skin. In contrast, ablepharon is the absence or severe hypoplasia of the eyelids. Affected individuals require surgical intervention in order to protect and cover the ocular surface. Ankyloblepharon is the fusion of part, or all, of the upper and lower eyelid margins as a result of incomplete separation during embryologic development. Presentation may vary from a few connecting bands to complete fusion of the eyelids. Mild cases in which only a few webs of adherent tissue are present may be treated in the clinician’s office using scissors to cut the aberrant tissue. More extensive intervention is indicated when the eyelid compromises the visual axis and there is concern for the development of amblyopia.

Eyelid Coloboma

An eyelid coloboma is a cleft or notch in the eyelid. These defects are typically an isolated finding in the upper eyelid. When located in the lower lid, colobomas may be associated with other congenital anomalies, such as Goldenhar syndrome. Infants with an eyelid coloboma are at high risk for the development of exposure keratopathy and often require surgical intervention.

Ectropion and Entropion

Ectropion is eversion of the eyelid margin. Congenital ectropion is caused by a vertical deficiency of the eyelid’s connective tissue (tarsal plate) or muscle (orbicularis oculi) and occurs more commonly in the lower eyelid. Congenital ectropion only rarely occurs as an isolated finding; more commonly, it is associated with ichthyosis, Down syndrome, or other midface developmental anomalies. In contrast to ectropion, entropion is inversion of the eyelid margin. Congenital entropion does not resolve spontaneously, and intervention is indicated for cases in which the ocular surface is exposed or otherwise compromised by in-turning of the lashes.

Epiblepharon

Epiblepharon is a congenital eyelid anomaly in which skin and pretarsal muscle overlie the eyelid margin to create an accessory horizontal fold of tissue. It occurs more commonly in the lower eyelid and in children of Asian descent. This condition is often asymptomatic. Rarely, the eyelashes may be misdirected toward the ocular surface and cause ocular irritation, tearing, and excessive mucus formation. Unlike congenital entropion, epiblepharon usually resolves spontaneously within the first few years of life as the facial bones mature. Conservative treatment with ocular lubricants is often sufficient therapy; however, surgical intervention is indicated if symptoms are severe or fail to improve.

Distichiasis

Some children are born with an accessory row of eyelashes, a finding known as distichiasis. These aberrant lashes grow out of the meibomian gland orifices and are typically thinner, shorter, and softer than normal cilia. These abnormal eyelashes are often asymptomatic. If patients show signs of ocular irritation, treatment may include cryoepilation, electrolysis, or surgical excision.

Epicanthal Folds

An epicanthal fold refers to an accessory vertical fold of skin covering the inner canthus. It is a common diagnostic sign in several syndromes (eg, Down syndrome, Zellweger syndrome, fetal alcohol syndrome, Turner syndrome). One should note that there are different types and severities of epicanthal folds and that they may be an isolated finding (Fig. 579-1). Epicanthus tarsalis is a vertical fold of skin more prominent in the upper eyelid. This finding is common in children of Asian ancestry. Epicanthus inversus is a vertical fold that is more prominent in the lower eyelid. Epicanthus palpebralis is a vertical fold that is distributed equally between the upper and lower eyelids. Finally, epicanthus supraciliaris is a vertical fold beginning at the eyebrow and extending inferiorly to the lacrimal sac. A variety of surgical techniques have been described to address these folds when needed.

As mentioned previously, the lateral canthus is approximately 1 mm higher than the medial canthus in the normal eyelid, giving the appearance of a slight upward slant. This slant may be exaggerated in some patients or even inverted, with the lateral canthus positioned lower than the medial canthus. There are wide variations in the appearance of palpebral fissure slants among ethnicities, and a slight upward or downward sloping is not uncommon. An exaggerated upward or downward slant may be associated with an underlying condition, such as an exaggerated downward palpebral fissure slant in Treacher Collins–Franceschetti syndrome (Fig. 579-2).

Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) refers to a constellation of eyelid and mid-face findings that include blepharophimosis, epicanthus inversus, telecanthus, and blepharoptosis (Fig. 579-3). It is also referred to as congenital eyelid syndrome or blepharophimosis syndrome. In this condition, there is shortening of the horizontal and vertical palpebral fissures (blepharophimosis) with poor levator function and an epicanthal fold greater in the lower eyelid. It may be sporadic or inherited in an autosomal dominant fashion. Typically these patients require ptosis repair early in life in order to prevent amblyopia. Repair of epicanthus and telecanthus is often purposely delayed, as these may improve to a certain degree as the child ages. A variety of techniques have been described to treat the telecanthus and epicanthal abnormalities.

PTOSIS

Ptosis, short for blepharoptosis, refers to a drooping upper eyelid (Fig. 579-4). It may be classified by timing of onset (congenital or acquired) and by etiology (myogenic, aponeurotic, neurogenic, mechanical, or traumatic). It is important for the clinician to identify the etiology of the ptosis and identify any life-threatening associations.

Myogenic Ptosis

Congenital myogenic ptosis results from embryologic dysgenesis of the levator palpebrae superioris. The poorly developed muscle is composed primarily of fibrous and adipose tissue and functions poorly as a retractor. Timely treatment of the ptosis with surgical repair is necessary in these children when the lid position blocks the visual axis. The specific technique used varies based on the degree of ptosis and the function of the levator muscle. Acquired myogenic ptosis, in contrast, may be seen in muscular diseases such as muscular dystrophy or chronic progressive external ophthalmoplegia.

Aponeurotic Ptosis

Aponeurotic ptosis results from stretching or a dehiscence of the levator aponeurosis, the fibrous ligament that connects the levator muscle to the tarsus. Because the levator aponeurosis is responsible for creating the upper eyelid crease, these patients typically have a high or absent upper eyelid crease with good levator function.

Neurogenic Ptosis

Neurogenic ptosis results from a disruption of the neuronal elements controlling the upper eyelid position, either cranial nerve (CN) III (oculomotor nerve) or the sympathetic chain. Congenital neurogenic ptosis may be the result of dysgenesis of CN III or the sympathetic nervous chain or caused by aberrant innervation between multiple cranial nerves. Congenital CN III palsy manifests as ptosis combined with an inability to elevate, depress, or adduct the globe. The ipsilateral pupil may or may not be dilated. Congenital Horner syndrome classically presents as a triad of ptosis, miosis, and anhydrosis. The ipsilateral iris is often hypopigmented. Ptosis in Horner syndrome is secondary to dysfunction of the sympathetic Müller muscle. This accessory eyelid muscle is responsible for only 1 to 2 mm of eyelid elevation; thus ptosis in Horner syndrome is typically mild and rarely visually significant but can be easily missed. Occasionally congenital neurogenic ptosis may be caused by aberrant connections between cranial nerves. Marcus Gunn jaw-winking syndrome is a congenital synkenesis between CN III and the motor division of CN V. In this condition, the ptotic eyelid retracts when the mandible is moved to the contralateral side. Nursing mothers are commonly the first to notice this phenomenon, and it is easily verified in the clinician’s office using a bottle or pacifier.

In acquired neurogenic ptosis, the nervous system develops normally but sustains an insult after birth. It is important to recognize acquired neurogenic ptosis because it may signify a lesion compressing CN III or the sympathetic chain that may be life-threatening, such as an aneurysm or neoplasm. Anisocoria, diplopia, ocular motility defects, neck pain, and headache in combination with ptosis are highly suggestive of a compressive lesion and warrant urgent neuroimaging.

Evaluating the Pediatric Patient with Ptosis

When evaluating a patient with ptosis, it is important to obtain a thorough history including onset, severity, associated signs and symptoms, and variability. The physical exam should focus on the lid crease height, amount of ptosis, and levator function. As mentioned previously, an absent or reduced upper eyelid crease is often found in congenital aponeurotic ptosis. The amount of ptosis may be quantified by measuring the distance between the center of the pupil and the upper eyelid margin. This measurement, commonly referred to as the margin-reflex distance (MRD), may be obtained by having the patient look at a light source in primary gaze and measuring the distance between the pupillary light reflex and the upper eyelid margin. A normal MRD is 4 to 5 mm. To evaluate levator function, firmly place a finger on the patient’s brow to prevent accessory eyelid retraction by the frontalis and measure the difference in eyelid position from downgaze to upgaze. A normal levator function is 13 to 17 mm.

Pseudoptosis

It is important for the clinician to distinguish true ptosis from pseudoptosis, in which the eyelid appears to be abnormally low because of an underlying finding. Pseudoptosis may be caused by various conditions, such as hypertropia, enophthalmos, microphthalmos, asymmetric eyelid skin, subcutaneous masses such as capillary hemangioma or plexiform neurofibroma, or retraction of the contralateral eyelid (as would occur with proptosis).

INFECTIOUS AND INFLAMMATORY CONDITIONS OF THE EYELID

Chalazion

A chalazion is an acquired eyelid disorder characterized by obstruction of meibomian gland orifices with subsequent focal eyelid inflammation (Fig. 579-5). The meibomian glands are sebaceous glands located in the tarsus and secrete the lipid component of the eye’s tear film. When an orifice becomes blocked, the glandular contents are instead released into the surrounding tissues causing a localized, lipogranulomatous inflammatory response. Although the exact etiology has not been completely elucidated, there is some thought that Demodex may play an important role. Clinically, a chalazion appears as a palpable, well-defined subcutaneous nodule in the eyelid and may be associated with mild to moderate edema, erythema, and tenderness. Conservative therapy with warm compresses is often sufficient to unblock the meibomian orifices. If this fails, incision and curettage may be performed. Other modalities such as intralesional steroid injection have proven efficacious but pose the potential risk of hypopigmentation, atrophy, and vascular occlusions.

Hordeolum

In contrast to a chalazion, a hordeolum (or stye) is an acute infection of the eyelid’s sebaceous glands. Often the inflammation is localized to an eyelash follicle, and epilation may promote drainage and hasten the resolution of symptoms. Warm compresses and a topical antibiotic ointment are often sufficient therapy, and no specific medical therapies have been found to be a superior treatment to date.

Blepharitis

Similar to adults, children may also be affected by blepharitis, an inflammatory condition of the eyelid margin. Signs and symptoms include eyelid margin erythema, crusting, and meibomian gland inflammation and inspissation. Rarely, blepharitis may cause chronic conjunctivitis and corneal pathology. The mainstays of treatment are warm compresses, eyelid hygiene with baby shampoo, and topical antibiotic ointment. Severe cases may benefit from oral erythromycin as well as topical or systemic azithromycin.

Molluscum Contagiosum

Molluscum contagiosum is a poxvirus that manifests clinically as multiple, small (1–2 mm), pink, umbilicated papules that may appear on the eyelids. These lesions are a common and benign skin finding in children and typically resolve spontaneously. In severe cases or cases causing secondary conjunctivitis, incision and curettage of the central core may be performed. In the appropriate setting, these lesions can be the initial presenting finding in patients with an immunocompromised status, such as human immunodeficiency virus or acquired immunodeficiency syndrome.

Preseptal and Orbital Cellulitis

Infections of the eyelid or periocular area are not uncommon. If the infection is restricted to the tissue anterior to the orbital septum, it is termed preseptal cellulitis. Clinically, the eyelids are edematous, erythematous, and warm to touch. Preseptal cellulitis is most commonly caused by trauma or underlying severe conjunctivitis. When assessing a patient with preseptal cellulitis, the clinician should obtain a thorough history, examine the eyelid for puncture wound or laceration, and inspect the underlying ocular surface to rule out adjacent pathology. If the infection is confined to the preseptal tissue, the patient may be treated with oral antibiotics as an outpatient with close follow-up. However, it is of paramount importance to differentiate preseptal from orbital cellulitis, as the latter requires hospitalization, intravenous antibiotics, and, in rare cases, surgical drainage of abscesses. Ocular dysmotility, proptosis, an afferent pupillary defect, or conjunctival chemosis suggests orbital involvement. The clinician should have a low threshold for inpatient observation of children with preseptal cellulitis, particularly if the patient is less than 1 year old or has signs of systemic illness.

OTHER EYELID ABNORMALITIES

Trichotillomania

Sometimes pediatric eyelid abnormalities are self-inflicted. Trichotillomania is an impulse-control disorder characterized by the repeated desire to pull out one’s hair, most commonly from the scalp but often the eyelashes or eyebrows. Patients characteristically present with madarosis, broken hairs, and hairs regrowing at different lengths. Trichotillomania is most commonly seen in preadolescence to young adulthood.

EPITHELIAL AND APPENDAGE TUMORS OF THE EYELID

Papilloma, Syringoma, and Hidrocystoma

Numerous eyelid lesions arising from epidermal, dermal, or adnexal structures may be present in children, with the vast majority of these being benign in nature. Three common eyelid and appendageal tumors found in children are papillomas, syringomas, and hidrocystomas. A papilloma is a pink, pedunculated or sessile mass associated with the human papillomavirus (HPV) that commonly occurs on the face and eyelid. These lesions are typically asymptomatic but are sometimes removed for cosmetic reasons. A syringoma is a benign neoplasm arising from eccrine sweat glands that typically affects young females. Syringomas manifest clinically as multiple small, skin-colored, waxy nodules clustered on the lower eyelid, often becoming more pronounced during puberty. There is an increased incidence in Asians, patients with Down syndrome, and females. A hidrocystoma is a smooth, translucent, skin-colored cyst arising from apocrine or eccrine glands on or near the eyelid margin. It transilluminates well when examined with a penlight. Superficial hidrocystomas are treated with marsupialization, while deep cysts require excision if the cosmetic appearance is bothersome to the patient.

Juvenile Xanthogranuloma

Juvenile xanthogranuloma (JXG) is a benign, non–Langerhans cell histiocytosis that may affect infants and young children. JXG appears as a single or multiple red-orange papules on the head and neck and may involve the eyelids. These lesions typically resolve spontaneously over the first few years of life. In some patients, JXG may have extracutaneous involvement. A small percentage of patients have intraocular lesions that are associated with significant ocular morbidity, such as spontaneous hyphema and secondary glaucoma. Although routine ophthalmic screening for all patients with JXG is not recommended, those with high-risk features such as multiple skin lesions or presentation at age 2 years or younger are at an increased risk of ocular morbidity and should be referred to an ophthalmologist.

VASCULAR MALFORMATIONS OF THE EYELID

Capillary Hemangioma

A capillary hemangioma is a benign vascular proliferation that may occur on the eyelid (Fig. 579-6). It is sometimes present at birth but more commonly appears gradually over the first weeks to months of life. If left untreated, these neoplasms may proliferate rapidly to compromise the visual axis and lead to amblyopia. β-Blockers have become the gold standard of treatment for these lesions. Some superficial capillary hemangiomas may be treated with topical timolol gel, while more extensive and deep lesions typically require systemic propranolol. For patients who do not respond to β-blockers or in whom their use is contraindicated, intralesional or oral corticosteroids may be beneficial.

Nevus Flammeus

Other congenital vascular malformations may also affect the eyelid. A port-wine stain, also referred to as nevus flammeus, is a prominent, benign cutaneous lesion often on the forehead and upper eyelid composed of numerous dilated capillaries in the dermis. The lesion first appears as a flat, red or pink patch that may darken to a deep red or purple. Over many years, it may thicken and become more nodular. If the lesion involves the eyelid or periocular area, the child is at a markedly increased risk for the development of juvenile glaucoma and should be referred to an ophthalmologist for evaluation. Although port-wine stains may occur in isolation, they are also associated with Sturge-Weber syndrome and Klippel-Trénaunay-Weber syndrome. Laser therapy or intense pulsed light have been shown to reduce the thickness and color of these lesions in many patients.

MELANOCYTIC ABNORMALITIES OF THE EYELID

Congenital Nevi

Congenital nevi are common on the eyelid and are often found on the eyelid margin or adjacent to it. In children, these lesions typically present as flat, pigmented macules. As the child ages, these lesions often become darker, thicker, and larger in diameter, particularly around the time of puberty. These lesions are typically benign and only rarely undergo malignant transformation. Although these lesions rarely transform into a malignant melanoma, patients with any changes should be referred to an ophthalmologist for evaluation.

Blue Nevus

A blue nevus is a dark bluish-gray, dome-shaped papule arising from dermal melanocytes. They typically do not grow larger than 10 mm in diameter. Although blue nevi have an extremely low malignant potential, these lesions warrant excisional biopsy to rule out the similar-appearing melanoma.

Oculodermal Melanocytosis

Another pigmented ocular adnexal lesion seen in childhood is oculodermal melanocytosis, or the so-called nevus of Ota. This congenital hyperpigmentation involves the periocular skin, often in the distribution of the first and second divisions of CN V. It occurs more commonly in patients of African, Hispanic, or Asian descent. The eyelid and periocular skin appear slate gray or dark blue. Affected patients commonly have pigmentation on the ipsilateral episclera and uvea. Patients with scleral or uveal involvement have an increased risk of malignancy, with 1 in 400 patients developing uveal melanoma over the course of a lifetime. Currently, there is no treatment or intervention to prevent malignant transformation.

ORBITAL LESIONS AFFECTING THE EYELID

Dermoid Cyst

Children may present with orbital lesions affecting the eyelids or periocular area. The most common orbital mass in childhood is a dermoid cyst. This benign lesion commonly presents as a slow-growing, palpable, painless mass in the area of the lateral brow and may alter the shape of the eyelid. It may be freely mobile or fixed to the underlying periosteum. Dermoid cysts are often removed surgically to prevent compression of the globe or severe inflammation as can happen with rupture. Although they are benign, workup with computed tomography or magnetic resonance imaging in certain cases can be useful to differentiate dermoid cysts form other lesions that may occur in the superotemporal orbit, such as an encephalocele or hemangioma. Imaging is also useful for measuring the degree of extension into the orbit or intracranial space.

Rhabdomyosarcoma

Rhabdomyosarcoma is the most common primary malignant orbital neoplasm in children. It is a rapidly progressive, highly malignant tumor of mesenchymal origin. Orbital rhabdomyosarcoma characteristically presents as acute, painless unilateral proptosis with displacement of the globe. The most common location is the superior orbit, and it frequently results in proptosis. Clinical suspicion for rhabdomyosarcoma warrants urgent imaging. Biopsy is required for diagnosis. The mainstay of treatment is chemotherapy and radiation, with the prognosis being relatively good depending on the subtype.

Metastatic Orbital Tumors in the Pediatric Population

Metastatic orbital tumors may also present with eyelid findings. The most frequent metastatic orbital tumor in children is neuroblastoma. It classically presents with unilateral or bilateral proptosis and eyelid ecchymosis. Primary tumor cells most commonly originate from the adrenal glands or sympathetic ganglion within the retroperitoneum or mediastinum. Consequently, patients may also complain of abdominal fullness or shortness of breath. Lymphoproliferative lesions such as leukemia and lymphoma, although relatively uncommon, may likewise present with proptosis, eyelid edema, and periorbital ecchymosis.

THE LACRIMAL SYSTEM

The lacrimal drainage system provides a conduit for tears to drain into the nasal passageways. It is composed of the upper and lower puncta, the lacrimal canaliculi, the lacrimal sac, and the nasolacrimal duct. The puncta are located near the nasal border of both upper and lower lids near the medial canthus. The puncta connect to the lacrimal canaliculi, the lacrimal sac, and finally the nasolacrimal duct, which drains into the nose. Any obstruction or inappropriate functioning of this intricate system can lead to tearing, discharge, and infection.

NASOLACRIMAL DUCT OBSTRUCTION

Congenital nasolacrimal duct obstruction has been estimated to occur in as many as 20% of newborns and is most commonly the result of an imperforate valve of Hasner blocking tears from entering into the nose. The clinical presentation typically includes mucoid or mucopurulent discharge and epiphora. The majority of nasolacrimal duct obstructions will resolve within the first 12 months of life, and lacrimal massage has been shown to increase the rate of clearance. In the event that digital massage does not clear the obstruction, a variety of surgical methods have been utilized to treat the problem with very good success.

Rarely, a nasolacrimal duct obstruction can result in an acute or chronic dacryocystitis. This infection can lead to a preseptal cellulitis or, less commonly, an orbital cellulitis. These pediatric patients should typically be admitted for intravenous antibiotics.

DACRYOCYSTOCELE

A dacryocystocele, also known as a mucocele or amniotocele, is a form of a congenital nasolacrimal duct obstruction that typically presents as a bluish, cystic, raised lesion inferior to the medial canthus. Some of these lesions will resolve either spontaneously or with digital massage, but others become infected, resulting in a dacryocystitis. Bilateral cases have been found to cause respiratory distress in some newborns; such lesions require urgent intervention, typically in the form of marsupialization of the nasal component and probing with or without silicone tubing for the upper component.

SUGGESTED READINGS

INTRODUCTION

The anterior segment of the eye consists of the cornea, the anterior chamber, the iris, the pupil, and the lens, which anatomically divides the anterior segment of the eye from its posterior segment. The posterior segment includes the vitreous gel, the retina, the optic nerve, and the choroid. This is a useful clinical division, because many diseases of the eye predominantly affect the anterior or posterior segment and are usefully differentiated from conditions (eg, endophthalmitis) that affect the whole eye. Casual inspection of the eye (the globe) is inevitably an assessment of the anterior segment structures and offers very little information about the internal, more posterior ocular structures. A checklist of anterior segment findings that may be recognized by the pediatrician would include cornea size and transparency; iris color (eg, heterochromia); pupil size, shape, position, and reaction to light; lens clarity (eg, cataract) and position (eg, dislocation/subluxation); and signs of elevated eye pressure.

CORNEA

Transparency of the cornea can be judged by how well the iris can be visualized and by noting the appearance of the normally black pupil. Comparing the patient’s cornea with those of a sibling or parent can be helpful. A cloudy cornea (Fig. 580-1) is always a significant clinical observation and has many pathologic causes (Table 580-1). Corneal transparency is essential for normal vision, and its loss is an important cause of childhood blindness. Corneal opacification and change in the cornea’s size are essential signs of both systemic and ocular disease. Some corneal conditions that cause cloudiness are best treated promptly, such as glaucoma and corneal keratitis (inflammation or infection of the cornea). Glaucoma in young children causes corneal cloudiness and enlargement (see Fig. 580-1), as well as optic neuropathy, potentially associated with permanent vision loss.

The corneas are normally transparent and equal in diameter. Rapid growth occurs in infancy, reaching adult size of 12 mm in horizontal diameter by 24 to 36 months of life. A cornea with a diameter greater than 13 mm is considered enlarged, and a diameter less than 10 mm is considered small. These abnormalities are more easily appreciated when the 2 corneas differ in size; this is always abnormal and requires immediate investigation (Table 580-2).

Symptoms of corneal disease vary considerably. Acquired defects of the corneal epithelium produce intense pain associated with photophobia and tearing. Corneal tears secondary to continued corneal stretching from elevated intraocular pressure are associated with intense photophobia and discomfort. Systemic diseases associated with cornea deposits of storage material are typically asymptomatic. Corneal enlargement secondary to glaucoma can also be asymptomatic.

ANTERIOR CHAMBER

The anterior chamber is filled with aqueous humor, which is optically clear. This space is delineated anteriorly by the back surface of the cornea and posteriorly by the iris and the front surface of the lens. It is best examined with a slit beam of light, which is a routine component of ophthalmologic examinations. The slit beam from an ophthalmoscope or a handheld slit lamp can be substituted when children are examined. Common abnormalities of the anterior chamber are shown in Table 580-3.

IRIS

Abnormalities of the iris and pupil are listed in Table 580-4. The iris (from Greek, iris means “rainbow”) is normally easily seen through the clear cornea and anterior chamber. It is variably colored from blue to dark brown, depending on the amount of melanin present. This pigmentation is normally uniform and approximately equal bilaterally. The architecture of the iris stroma making up the body of the iris is highly variable and is studied carefully by ophthalmologists for evidence of intraocular disease.

The pupils are usually approximately equal in size; they enlarge (dilate) in reduced illumination and constrict in response to increased light or with accommodation. Careful assessment of pupillary reactivity to a light stimulus is an important test of ocular and optic nerve function as well as a test of third nerve function. If pupil size is asymmetric, it is important to determine which is the abnormal pupil. If the relative disparity increases in bright light, the larger pupil is abnormal (ie, not constricting properly). If the disparity increases in dim light, the smaller pupil is abnormal (ie, not dilating properly). If the relative disparity is maintained regardless of the illumination, the child has physiologic anisocoria, a finding seen in approximately 20% of the normal population. Examination of old photographs may be useful in establishing the congenital nature of this minor anomaly.

Arguably the most important pediatric pupillary eye sign is leukocoria, the white pupillary reflex, also referred to as the cat’s eye reflex (Fig. 580-2). This defect is caused by the reflection of light from a white cataract or from a white structure in the posterior segment. Many defects produce this reflex, including cataract, retinoblastoma, and retinal detachment. The expected “red reflex” is the normal reflection from the vascular choroid underlying the retina. It is rarely actually red but more often a combination of yellow, pink, and orange. Most importantly, it is symmetric between the 2 eyes. An absent red reflex (“black reflex”) is also a sign of intraocular disease, indicating an obstruction in the ability of light to reach and reflect back from the inner eye. Possible causes include cataract and presence of blood, but it is commonly merely the result of miosis (small pupils); pharmacologic dilation of the pupils may reveal a normal red reflex and obviate the need for referral. An absent reflex or leukocoria should prompt urgent referral for ophthalmology consultation.

DISORDERS AFFECTING THE ANTERIOR SEGMENT

The most important and vision-threatening diseases of the anterior segment are keratitis, glaucoma, and cataracts. Both glaucoma and cataracts may be inherited, are associated with many pediatric systemic conditions, and can be secondary to other eye conditions such as trauma or chronic ocular inflammation. In developed nations, they are the most important causes of preventable and treatable blindness.

CHILDHOOD GLAUCOMA

Childhood glaucoma is an uncommon eye disease but an important cause of blindness. Potential causes fall into 1 of 2 categories: primary (isolated) glaucoma or glaucoma secondary to some other ocular disease (Table 580-5). Primary congenital glaucoma is caused by abnormal development of the aqueous humor drainage system. It occurs in about 1 in 10,000 births in the United States and is the most common form of glaucoma in infants. Secondary glaucoma results from other disorders of the eye and may or may not be genetic; these include cataract surgery, trauma, or uveitis. Both types may be associated with other medical conditions. Ten percent of primary congenital glaucoma is present at birth, and 80% is diagnosed during the first year of life. The first signs of glaucoma include clouding or enlargement of the cornea (see Fig. 580-1). The elevated intraocular pressure can cause the eyeball to enlarge, with injury to the inner layers of the cornea (Haab striae). Important early symptoms of glaucoma in infants and children are blepharospasm (frequent blinking), light sensitivity, and tearing. The prognosis for vision is directly related to early recognition and treatment and to the severity at presentation.

Treatment of glaucoma in children is different from that in adults. Many patients will require surgery, with the goal of reducing pressure either by increasing the outflow of fluid from the eye or decreasing the production of fluid within the eye. Goniotomy or trabeculotomy are important surgical procedures that open the natural drainage mechanism (the trabecular meshwork) of the eye. Goniotomy is preferred, as it is less injurious to the eye tissues. Its rate of success is associated with the age of the child at the time of diagnosis, the type and severity of the glaucoma, and the surgery technique. Other surgical options are trabeculectomy and insertion of glaucoma drainage tubes, both of which create alternative means for fluid to escape from the eye.

Approximately 80% to 90% of babies who receive prompt surgical treatment, long-term care, and monitoring of their visual development will do well. If childhood glaucoma is not recognized and treated promptly, permanent visual loss will result. Unfortunately, primary and secondary congenital glaucoma still causes 2% to 15% of blindness in children.

CHILDHOOD CATARACT

The natural lens of the eye anatomically forms the normally clear, transparent back wall of the anterior segment. It provides approximately 20% of the total focusing power of the eye with the remainder being supplied by the front surface of the cornea. Pathologic lesions of the lens include opacification (cataract formation), dislocation or subluxation (ectopia lentis), and abnormalities of size. The lens is normally clear, but frequently small stable opacities can be identified; these are of no visual significance and do not require treatment. The lens is a highly cellular structure that continues to grow into adult years. It is metabolically active and at risk for the formation of cataracts related to many primary and secondary mechanisms (Table 580-6).

Cataracts in children are not rare, occurring with an incidence of approximately 1 per 4000 to 10,000 children. The red reflex test is an important screening tool to help recognize cataracts. Cataracts may be focal or total (see Fig. 580-2), unilateral or bilateral, and congenital or acquired and are an important cause of childhood blindness. Early recognition is essential to allow prompt intervention and optimal outcome for vision. Recognition of cataracts can be an important diagnostic aid in interpreting systemic inheritable diseases and acquired conditions.

Treatment of childhood cataracts that are visually significant requires their removal and correction of the resultant optical defect. Optical correction is accomplished with intraocular lenses, contact lenses, or spectacles; effects of these techniques on outcome for vision appear to be similar. Different centers may have different cutoffs for implanting an intraocular artificial lens, but in general, most centers will not do so until a child is 1 to 2 years old. Spectacles are quite thick and often cosmetically unsatisfactory, but in infancy or early childhood, when appearance is less of an issue, they can be well-tolerated and result in excellent vision outcomes. For many years, contact lenses have been the “gold standard” for visual rehabilitation in infants who have had cataract surgery. The lenses are usually made of highly permeable silicone that can allow for some long-term use, but daily wear is preferred. Parents can become remarkably adept at contact lens insertion and removal. Limitations include cost, convenience, and availability from the manufacturers.

Lens dislocation/subluxation (ectopia lentis) may be an isolated defect but more frequently occurs in association with an ocular disease (eg, aniridia) or secondary to a systemic disease (eg, Marfan syndrome). Dislocation of the lens occurs in all instances due to loss of zonular integrity: secondary to a genetic defect or due to stretching in the case of an enlarged eye (eg, congenital glaucoma). A subluxed lens can cause high refractive defects, decreased vision, ocular inflammation (iritis), and glaucoma (see Table 580-5). Early lens subluxation may require only optical correction (glasses or contact lenses), but when vision is more significantly affected, surgical removal of the lens may become indicated. Homocystinuria is a rare cause of ectopia lentis that must be ruled out by appropriate serum or urine testing prior to surgery in any child in whom another cause of the ectopia lentis cannot be confirmed. Children with homocystinuria have a platelet aggregation defect that can lead to thromboembolism during anesthesia.

KERATITIS

Infection of the cornea is a serious vision-threatening disorder that requires urgent ophthalmology consultation, particularly if bacterial or herpetic infection is suspected. Bacterial ulcers appear as white areas overlying the iris or pupil. Patients usually have intense pain and photophobia. Bacterial infection is most common in contact lens wearers. For that reason, the pediatrician, faced with a child who presents with a red and painful eye and who wears contact lenses, should remove the contact lens; instilling a topical anesthetic such as tetracaine or proparacaine may facilitate removal. The child should be referred to an ophthalmologist urgently. The pediatrician should not put the child on antibiotics and should not apply a patch. The ophthalmologist will first determine if the symptoms and signs are due to infection or to other contact lens–related issues (eg, overwear, contact lens solution allergy, tight fit). If an infectious corneal ulcer is present, direct culture may be required and an intense broad-spectrum antibiotic regimen started. Contact lens wearers increase the risk for infection by overnight wear, poor hygiene, swimming in fresh water with contact lenses on, or using tap water for cleaning the lenses.

Herpetic infection can result from herpes simplex or varicella. Primary dermatologic infection is usually not associated with corneal involvement, but the presence of a red eye should prompt urgent ophthalmology consultation. Subsequent recurrence may be confined to the cornea with or without involvement of surrounding skin. Episodes are usually painful and almost always unilateral. Patients learn to recognize their symptoms and intensely red eye. Antiviral treatment should be prescribed only by an ophthalmologist, who will provide ongoing care. Scar formation may lead to vision loss, which may even require corneal transplantation.

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INTRODUCTION

Retinopathy of prematurity (ROP) is a disorder that affects the developing retinal blood vessels of premature infants. It is the leading cause of both acquired and preventable childhood blindness in the United States. The disease was first recognized in the 1940s and was initially thought to be due to the normal primitive vascular system in the vitreous cavity persisting in an abnormal fibrotic state. By 1952, ROP became recognized as an acquired disease, and in 1955, the role of excessive supplementary oxygen for premature infants was proven to be a significant causative factor. Despite many improvements in neonatal care practices, ROP continues into the 21st century as a major complication of premature birth.

EPIDEMIOLOGY

ROP occurs almost exclusively in premature babies, especially those born below a gestational age of 31 weeks or a birth weight below 1500 g. The development of ROP usually correlates with the overall extent of medical illnesses and complications associated with prematurity, such as intraventricular hemorrhage, necrotizing enterocolitis, sepsis, bronchopulmonary dysplasia, patent ductus arteriosus, acidosis, anemia, and blood transfusion. Medical risk factors are dominated by the fact that the incidence and severity of ROP increase inversely with birth weight and gestational age. Full-term infants rarely, if ever, develop significant ROP.

In the data from the Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) study, black infants demonstrated 65% lower odds of reaching severe ROP in need of treatment. The reason for this is unclear, but genetic influences are a possibility. In addition, there are relatively rare genetic disorders of the eye with similarities to ROP, including familial exudative vitreoretinopathy (FEVR), Norrie disease, and incontinentia pigmenti. The main pediatric retinal vascular diseases to distinguish from ROP are considerably rarer than ROP. Premature infants at risk for ROP typically undergo routine ophthalmologic examination, so, in general, the ability to observe the classical appearance and development of ROP allows a firm diagnosis.

In the United States, problematic ROP is limited to infants with birth weights less than 1500 g. As of the early part of this millennium, the average birth weight for US infants requiring treatment for ROP is about 700 g. ROP occurs in about 60% of infants born weighing 1500 g or less. In that same group, about 5% require treatment.

PATHOPHYSIOLOGY

In utero, the normally developing human retinal vasculature proceeds centrifugally outward from the optic nerve head, reaching the ora serrata on the nasal side of the eye by about 36 weeks, and the temporal ora serrata at the full gestational term of about 40 weeks. Premature birth occurs at a time when there is incomplete vascularization of the retina. In ROP, extrauterine factors perturb the finalization of this vascularization process, interrupting normal vessel growth and sometimes leading to a cascade of disruptive events.

Although supplemental oxygen administration plays a role in the pathogenesis of the disease, it is not a necessary prerequisite. No precise level of supplementary oxygen has been demonstrated as safe in the treatment of premature infants. Balancing the risk of ROP against the risk of brain injury from hypoxia has been a chronic challenge for neonatologists. Normally, fetal blood is only about 70% saturated compared to 100% in full-term infants breathing room air. The usual prenatal PaO₂ is 30 mm Hg, while a normal infant in room air will have a PaO₂ of 60 to 100 mm Hg. This relative hyperoxia of the extrauterine environment, combined with supplemental oxygen, is thought to initiate abnormal vascular development in the premature infant.

ROP progresses in 2 phases: the hyperoxic phase (phase I) and the ischemic phase (phase II). In phase I, exposure of the preterm infant to the relatively hyperoxic extrauterine environment after birth leads to downregulation of vascular endothelial growth factor (VEGF) production and cessation of vessel growth. As the infant matures, the density of blood vessels in the retina becomes too small to maintain the increasing metabolic demand, and therefore tissue hypoxia occurs, initiating the onset of phase II. Hypoxia signals the upregulation of VEGF and other angiogenic factors, leading to abnormal vessel proliferation typical of ROP. Newer studies demonstrate that insulin-like growth factor 1 (IGF-1) and transforming growth factor β (TGF-β) also play a role, although exactly how is not clear.

CLINICAL FEATURES

Clinically, ROP is characterized by abnormally abrupt termination of the vascularized portion of the retina at a visible peripheral boundary, and it may progress through sequential development that may include extraretinal vasoproliferation, vitreous hemorrhage, and contracture of the vitreous body adjacent to the retina with traction on the retina and retinal detachment. Typically, both eyes follow a similar course, but some degree of timing and severity asymmetry occurs in approximately 15% of cases.

An International Classification of Retinopathy of Prematurity is used to quantitate the severity of ROP (Table 581-1). Abnormal findings are categorized by location, stage, and vascular pattern at the initial visit and at each follow-up visit (Fig. 581-1).

ROP starts appearing in some premature infants as early as 4 to 5 weeks after birth and typically reaches the need for laser treatment at mean gestational ages between 35 and 40 weeks, or at around 6 to 12 chronological weeks postnatally. High vigilance by the examining ophthalmologist is warranted during this critical developmental window.

In normal premature vascular development, the peripheral retinal vessels resemble tree branches and taper systematically toward the periphery of the retina; however, the clinical progression of ROP begins with a prominent abrupt circumferential boundary between the vascularized and nonvascularized retina. This intraretinal demarcation line is the first sign of ROP and is designated as stage 1 (Fig. 581-2). At any time in the early progression of ROP, the disease can spontaneously involute and allow normal retinal vascularization to complete itself. If ROP progresses from the simple demarcation line of stage 1, that line increases in volume and becomes elevated into a ridge (stage 2, Fig. 581-2). The ridge is comprised of a complex system of arteriovenous shunts. With further progression, the ridge develops a ragged appearance due to extraretinal neovascularization of the arborizing vessels that terminate at the ridge (stage 3). If the retina begins to lift off the underlying choroidal layer, this is a retinal detachment. Stage 4a is a partial retinal detachment sparing the macula, while stage 4b is a partial retinal detachment that includes the macula. Stage 5 is a total retinal detachment.

Progression of stage 3 ROP is associated with extension of the fibrovascular proliferation at the demarcation ridge into the vitreous cavity. This can lead to hemorrhage into the vitreous body, peripheral retinal fibrosis with tractional dragging of the vessels and macula, and retinal detachment. Typically, retinal detachment starts peripherally and may arrest as a partial detachment, but more likely it will progress to a total detachment of the retina. The end stage of uncontrolled ROP is a total, funnel-shaped retinal detachment with extensive fibrovascular proliferation within the vitreous space of the eye, leading to a white mass behind the lens and a whitish pupil (leukocoria). The older term retrolental fibroplasia (RLF) was derived from this appearance but is no longer used. All stages leading up to, and including, a total funnel detachment are today properly referred to as ROP.

Plus disease refers to a localized ocular vascular incompetence that can accompany all progressive forms of ROP. The retinal (Fig. 581-3), and often iris (Fig. 581-4), vessels in plus disease are dilated, tortuous, and unable to maintain the blood-retina barrier and may result in vitreous haze and pupillary rigidity. This vascular characteristic is the single most significant negative prognostic factor in ROP. It is a binary diagnosis—either “there” or “not there”—and yet its determination is clinically subjective. The degree of dilation and tortuosity must meet or exceed a reference standard: a photograph that has been used in collaborative ROP clinical trials. It appears at a mean gestational age of about 35 weeks. Lesser degrees of dilation and tortuosity are called pre-plus disease.

The anteroposterior location of ROP reflects the degree of maturity of retinal vascularization at the time ROP sets in. Less mature eyes have more posterior ROP, and more posterior ROP has a worse prognosis. The International Classification of Retinopathy of Prematurity (ICROP) defines this variable according to 3 zones. The most posterior zone for ROP is labeled as zone I, and its boundary is a circle centered at the optic disc, with a radius equal to twice the distance from the disc to the fovea. The more peripheral and anterior zone II extends out to another virtual boundary conceived as a larger concentric circle that ends at the farthest extent of retina (the ora serrata) on the nasal side of the eye. Due to the larger area of retina that exists temporal to the optic disc, this leaves a mostly temporal crescent of retina defined as zone III. While ROP can occur in both zones I and II in a given eye, by convention, zones II and III are mutually exclusive, and the decision is based on the findings in the far nasal periphery. Most ROP occurs in the intermediate zone II. The best prognosis is with ROP located in zone III, and necessity for treatment of zone III ROP is quite rare.

A more rapid pace of ROP progression is associated with worse prognosis. Rapidly progressive ROP was once loosely referred to as rush disease, but this ill-defined term has been abandoned in favor of the phrase aggressive posterior ROP (AP-ROP), which emphasizes the location and ominous nature of the ROP without implying a particular velocity of progression.

DIAGNOSTIC EVALUATION

Table 581-2 summarizes the 2013 American Association of Pediatrics (AAP), American Academy of Ophthalmology (AAO), and American Association for Pediatric Ophthalmology and Strabismus (AAPOS) joint diagnostic examination screening guidelines for ROP. Early ocular fundus examinations are required for all infants with birth weights less than 1500 g, or with gestational age of 30 weeks or less. Larger, more mature infants should be included whenever special risk factors exist, such as those who received high amounts of supplemental oxygen or whose medical course was especially complicated, resembling that of less mature infants. The optimal time for the initial examination (general physical condition permitting) is at 31 weeks of postmenstrual age (PMA) or 4 weeks of chronologic age, whichever comes later. Generally, examinations are performed weekly or biweekly, as indicated by the rapidity and severity of the disease, until the retina is fully vascularized and any ROP that did develop has fully involuted. Great caution should be exercised in monitoring for ROP, in particular being conservative in determining intervals for examinations.

Currently there is investigational interest in screening for ROP by means of digital fundus photography, with the idea being to transmit images to an expert interpreter (presumably an experienced ophthalmologist) who can determine if a real-time examination by an ophthalmologist is necessary. This method could potentially enhance efficiency and decrease costs, but its safety has yet to be demonstrated in properly designed clinical trials. Additional investigations are under way to electronically diagnose the presence or absence of plus disease. Methods already exist to measure dilation and tortuosity of retinal vessels from images, but the transferability of this into safe clinical practice awaits further clinical studies.

Perhaps one of the greatest obstacles to successful outcomes is failure of follow-up after discharge from the hospital. While the patient is in the hospital, procedures are more easily put in place to ensure regular periodic examination. Similarly, procedures and practice in the outpatient setting must be enacted to continue the follow-up after discharge.

TREATMENT

Table 581-3 outlines the ROP severity categories used in major clinical treatment trials, based on the severity and extent of the disease. Until December 2003, eyes were treated when “threshold” criteria were met. Since then, it is now recommended to treat eyes with type 1 ROP.

The CRYO-ROP Cooperative Group demonstrated that applying cryotherapy to the entire nonvascularized peripheral retina in well-established threshold disease (stage 3 disease meeting specific criteria with plus disease) reduced the risk of adverse outcomes (macular dragging and retinal detachment) by 50%. Ablation of the nonvascularized peripheral retina eliminates biologic stimuli to the proliferation of vessels at the demarcation zone. Treatment was so effective that the study was stopped before completion.

In 2004, the Early Treatment for Retinopathy of Prematurity (ETROP) Cooperative Group showed that diode laser treatment aimed though the pupil, lens, and vitreous cavity and applied to the avascular retina further reduced the adverse structural outcomes of ROP and became the preferred treatment modality over cryotherapy. ETROP recommended treatment for so-called type 1 ROP, which includes zone I ROP of any stage in the presence of plus disease; zone I ROP with any stage 3 disease; and zone II ROP with stage 2 or 3 disease in the presence of plus disease. Definitions of type 1 are summarized in Table 581-3.

A newer treatment modality is the use of anti-VEGF antibodies injected into the vitreous cavity. In 2011, the BEAT-ROP study concluded that intravitreal bevacizumab is superior to laser in zone 1 with stage 3+, and equivalent to laser in posterior zone 2 with stage 3+, although this was not without controversy. Advantages of intravitreal anti-VEGF injections include faster treatment, lower cost, utility in patients with hazy media, and decreased incidence of severe myopia. Disadvantages include the risk of endophthalmitis, potential worsening of anterior ROP, potential for late reactivation necessitating longer follow-up, and most importantly, concerns over systemic absorption of anti-VEGF antibodies and their effect on other developing organ systems. Many studies are ongoing to look into these issues.

If laser treatment and/or intravitreal injection fail to prevent retinal detachment, then treatment by specialists in pediatric retinal surgery can be helpful in preventing total blindness. The more retinal area that has detached, the poorer is the prognosis, so urgent evaluation and treatment are of utmost importance.

SEQUELAE

End-stage ROP with stage 5 total retinal detachment can be associated with progressive shrinking of the eye (phthisis), corneal opacity, cataract, and glaucoma with or without pain. At this stage, blindness in the eye is a certainty. The eye may appear enophthalmic and may exhibit nystagmus.

Patients in whom involution/regression occurs without and especially with treatment may still develop sequelae such as myopia, amblyopia, and strabismus (ocular misalignment). For this reason, long-term follow-up is required.

PREVENTION

Prematurely born infants are at risk for ROP, and this risk increases with shorter gestation prior to birth. For each week of further gestation, there is a 19% reduction in the odds of developing severe ROP. All reasonable efforts to extend pregnancy toward full term are to be encouraged.

Many interventional treatment approaches have been employed to reduce ROP incidence and progression, including reduction of ambient light and the use of supplemental inositol and vitamins A and E, none of which have been definitively proven or disproven. Supplemental oxygen therapy, long known to be a potential causative factor in ROP, continues to be a vexing dilemma for neonatologists. There has been a trend toward further reduction of therapeutic oxygen supplementation in the early weeks of extrauterine life for premature infants, but the optimal dosage practice remains elusive and is the subject of ongoing clinical investigations. In 2015, a meta-analysis of 3 similar prospective studies (SUPPORT, BOOST II, and COT) concluded that infants stratified into a target oxygen saturation between 91% and 95% had decreased mortality and decreased incidence of necrotizing enterocolitis when compared to a group targeted between 85% and 89%. Although the incidence of ROP in the former group was higher, the incidence of structurally unfavorable ROP was equivalent. Thus, the current recommendation is to target oxygen saturation between 90% and 95% in all children still at risk for ROP unless certain cardiac diseases (requiring lower targets) or pulmonary hypertension (requiring higher targets) are present.

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INTRODUCTION

The development of techniques for identifying the genetic bases for disease has dramatically increased our understanding of eye diseases. The prevalence of genetic disease as the basis for significant visual loss is uncertain and a function of the population, healthcare resources, and cultural values. Genetic factors may influence development of the eye but also may cause a progressive deterioration over time. Although a specific mutation of a gene may result in a consistent phenotype, variation is common and may reflect the effect of other genes or environmental factors. Complex diseases, such as myopia and strabismus, probably have both genetic and environmental bases. Ascertainment bias, inconsistent data collection, or cultural factors influence population-based studies. Autosomal recessive disorders are more common in cultures with high rates of consanguinity (Middle East or Southeast Asia). Other disorders, such as the group of diseases called retinitis pigmentosa, have a more uniform geographic prevalence rate of 20 to 40 per 100,000 worldwide. With the completion of the Human Genome Project (http://www.ornl.gov/sci/techresources/Human_Genome/home.shtml) and the rapid development of improved analytical tools, a new understanding of the genetic bases of eye diseases offers the hope of understanding causes and identifying cures.

Mutations of genes expressed primarily or exclusively in the eye cause a multitude of diseases. Some disorders are multisystemic. A genetic basis should be identified for visual loss or malformations that are not attributable to infections or trauma to optimize both treatment of the patient and counseling of the family. The evaluation should be initiated with a careful family history and pedigree. The parents should be queried about consanguinity. It is helpful to identify the anomalies commonly encountered in genetic eye diseases and syndromes (eg, kidney abnormalities and general dysmorphic features such as abnormal interpupillary distance, epicanthal folds, and palpebral fissure slant). The ophthalmologist increasingly depends on the primary care physician to make an accurate diagnosis, and the primary care physician/geneticist depends on the ophthalmologist for information that may be helpful in rendering a diagnosis and prognosis. Consultation with a board-certified geneticist is wise. The European Union requires referral of patients with possible genetic diseases to a board-certified geneticist (Oviedo Convention, 1997, Treaty of Lisbon, 2009) in countries with such certification.

This chapter will deal with some genetic diseases of the eye. Cataract, glaucoma, and corneal diseases often have a genetic basis and are discussed in Chapter 580. Section 12 includes multisystem genetic disorders that have ocular manifestations (eg, neurofibromatosis in Chapter 176).

EMBRYOLOGY

Major structural anomalies occur in 2% to 3% of all newborns, and minor anomalies occur in 15%. The eye begins as a groove in the forebrain at 22 days of gestation. Histologically, the lens placode is evident by 4 weeks with a lens vesicle in the optic cups by 5 weeks. The groove on the ventral surface of the optic cup closes by 7 weeks, closing the optic nerve and completing the pupil. A major regulatory gene for eye development is PAX6 (paired box gene 6), a transcription factor; other important regulatory genes are the PAX2 (paired box gene 2) and SHH (sonic hedgehog) genes. Multiple gene products function in pathways downstream of each of these genes. Mutations in these and other genes can lead to eye disease.

CHROMOSOMAL DISORDERS

Most chromosomal disorders may be associated with abnormal eye findings, and virtually all involve other organ systems. Infants with chromosomal disorders often have multiple congenital anomalies, growth retardation, and developmental delay in addition to the ocular abnormalities. All microscopically identifiable chromosomal deletions, duplications, or aneuploidies (disorders of chromosomal numbers) are associated with some element of mental retardation, with the exception of some X-chromosomal anomalies. The ocular manifestations of chromosomal aberrations are numerous, varied, and beyond the scope of this chapter. Some examples of eye findings in chromosomal aberrations are listed in Table 582-1.

MONOGENIC DISORDERS

Monogenic disorders are caused by a mutation in a single gene. Some syndromes can be caused by mutations in more than 1 gene (genetic heterogeneity), each resulting in a similar syndromic phenotype, and may have variable inheritance patterns. Similarly, different mutations in the same gene can result in different phenotypes. Increasingly, known genes can be sequenced if the clinical diagnosis suggests a particular disease, thus allowing for a molecular diagnosis.

Online Mendelian Inheritance in Man (OMIM) is a continuously updated catalog of human genes and genetic disorders and traits, with particular focus on the molecular relationship between genetic variation and phenotypic expression. It is thus considered to be a phenotypic companion to the Human Genome Project. Because of the genetic heterogeneity of many of the syndromes discussed further in this chapter, we refer the interested reader to http://www.omim.org for a detailed insight into these disorders and their genotype.

Table 582-2 lists eye findings for many monogenic multisystem disorders. For further discussion of inborn errors of specific genes such as the mucopolysaccharidoses, sphingolipidoses, and mucolipidoses, refer to Section 11.

GENETIC EYE DISORDERS

Microphthalmia/Anophthalmia

Microphthalmia is a small eye (as differentiated from isolated microcornea). Anophthalmia refers to the complete absence of the eye; true anophthalmia is rare and can be confirmed only at autopsy based on orbital serial sections. Anophthalmia results when the optic vesicle fails to form. Primary anophthalmia and microphthalmia may occur in an otherwise normal child or in association with a multisystem disorder such as trisomy 13, deletion of the short arm of chromosome 18, or other cerebral maldevelopment disorders. Isolated anophthalmia usually occurs sporadically and may be due to autosomal dominant, autosomal recessive, and X-linked recessive mutations. SOX2 has been identified as a major causative gene. Other linked genes include PAX6, OTX2 (orthodenticle; drosophila; homolog of 2), CHX10 (visual system homeobox 2, VSX2), and RAX (retina and anterior neural fold homeobox gene).

Aniridia

The term aniridia is a misnomer, because a small stump of iris tissue is almost always present; the disorder is rarely limited to the iris malformation (Fig. 582-1). The original reports of the PAX6 mutation included an individual with normal irides. The malformation is usually an autosomal dominant disease. Expression can be extremely variable even within a family. Nystagmus (wandering or shaking eye movements), cataracts, ectopia lentis (dislocated lens), glaucoma, macular hypoplasia, optic nerve hypoplasia, and retinal dystrophy also may occur. The corneal epithelial stem cells may be abnormal, resulting in progressive vascularization of the cornea (pannus), which is associated with an increased risk of transplant rejection. Glaucoma develops before adolescence in approximately 50% of patients. Visually significant cataracts are common.

The “sporadic” form accounts for one-third of all cases and may be associated with a deletion of the short arm of 11p13. This region includes the PAX6 and Wilms tumor genes (WT1), and absence of the regional genes may result in genitourinary anomalies and mental retardation (WAGR syndrome [Wilms tumor; aniridia; genitourinary anomalies, usually tumors of the gonads; and mental retardation]). About 30% of patients with the chromosomal deletion form of aniridia develop a Wilms tumor before 3 years of age; this cancer is diagnosed before age 5 years in 80% of cases. Conversely, less than 2% of patients with Wilms tumor have aniridia. All patients with sporadic aniridia should have a karyotype, including assessment for a microdeletion using fluorescence in situ hybridization or microarray. Renal ultrasound study should be performed every 3 to 6 months to assess the possibility of Wilms tumor in all infants/children with sporadic aniridia, and every 3 months in those with deletions of chromosome 11. Aniridia has not been reported in families with autosomal dominant Wilms tumor.

A rare autosomal recessive form of iris deficiency (Gillespie syndrome) has a different iris appearance and is associated with other systemic abnormalities (cerebellar ataxia, mental retardation) not seen in typical PAX6 aniridia. There is also a rare variant of Axenfeld-Reiger spectrum with aniridia in the presence of posterior embryotoxon but with normal retina, no cataract, and no nystagmus.

Retinal Dystrophies

Retinitis pigmentosa is a general term for a group of hereditary retinal degenerative diseases and may include all genetic forms of retinal dystrophies/degenerations. Nyctalopia is the term describing reduced visual function under low lighting conditions. The rod cells of the retina primarily influence peripheral and night vision, and the cone cells are responsible for central vision (20/20 to 20/200) under lighted conditions; the fovea is a specific portion of the macula that is rich in cones and is the retinal region for sharpest vision. Thus, a disease that is primarily in the rods will be characterized by greater symptoms under low lighting conditions and an abnormal electroretinogram under darkened (dark-adapted) conditions. A disease that is primarily in the cones will produce decreased central visual acuity and be associated with an abnormal electroretinogram under lighted conditions. Isolated disease of the rod cells may cause cone degeneration and vice versa.

Retinitis Pigmentosa

Classically, retinitis pigmentosa is characterized by progressive peripheral visual field loss, nyctalopia, and pigmentary retinopathy; on laboratory testing, a depressed or nonrecordable electroretinogram and delayed dark adaptation are evident. The typical, late-stage fundus appearance consists of optic atrophy, retinal blood vessel attenuation, and “bone-spicule” pigmentary clumping (Fig. 582-2). Inheritance patterns include autosomal dominant, autosomal recessive, and X-linked recessive, with some proportional variation based on geography. Mitochondrial and X-linked dominant phenotypes also occur. Mutations in over 100 genes, with different functions, have been implicated in causing classic retinitis pigmentosa. The RetNet Web site (www.sph.uth.tmc.edu/RetNet/) is an excellent, up-to-date source for genes and mapped loci that cause retinal diseases. Approximately half of all affected individuals have no family history of the disease. Although early-onset forms do occur, most patients are not severely handicapped until adulthood. Autosomal recessive and X-linked forms tend to present at an earlier age than the autosomal dominant forms. Affected individuals should be screened regularly for ocular complications such as cataracts and edema/intraretinal cystoid spaces of the macular region.

Retinitis pigmentosa may be limited to the eyes, or it may be associated with additional organ system involvement such as congenital hearing loss in Usher syndrome. Retinitis pigmentosa also may be part of mitochondrial diseases.

Nongenetic conditions may produce a pigmentary disturbance of the retina similar to retinitis pigmentosa; these include metastatic cancer, intrauterine and perinatal infections (syphilis, rubella, cytomegalic inclusion disease, influenza), and drug toxicity (phenothiazines, chloroquine). Most are not progressive, and the electroretinogram is normal.

The genetic bases (genes) and specific mutations of genes that cause isolated retinal disease have increased rapidly, and up-to-date information is available at RetNet.

Congenital Stationary Night Blindness

Congenital stationary night blindness (CSNB) is usually characterized by nyctalopia that is evident in childhood. Based on electroretinography, a complete and incomplete form can be distinguished. Although both forms exhibit very similar signs and symptoms, the complete form more often has nyctalopia. This genetically heterogeneous disorder may be inherited in an autosomal dominant, autosomal recessive, or X-linked recessive pattern. The group of diseases underscores the variability of clinical features of different mutations of a specific gene. For example, an autosomal dominant form may be caused by mutations of the rhodopsin (RHO) gene that more commonly causes classic retinitis pigmentosa. Another autosomal dominant form is caused by mutations of the phosphodiesterase 6B, cGMP-specific, rod receptor, beta specific (PDE6B) gene that also causes retinitis pigmentosa. Mutations in the guanine nucleotide–binding protein and alpha-transducin activity polypeptide 1 (GNAT1) gene can also cause autosomal dominant CSNB. The autosomal recessive forms may be caused by mutations in 11 genes. For an up-to-date overview, consult the online source RetNet (www.sph.uth.tmc.edu/RetNet/). The X-linked recessive varieties may be caused by mutations of the nyctalopin (NYX) or retina-specific calcium channel alpha-1-subunit (CACNA1F) genes. Oguchi disease, an autosomal recessive disorder, has similar symptoms and is caused by mutations of the arrestin (SAG) gene or the rhodopsin kinase (GRK1) gene.

Usually, visual acuity is relatively good in the autosomal dominant forms but may be reduced earlier in life in the recessive and X-linked forms. Variable degrees of myopia with associated degenerative retinochoroidal changes may be detected. The clinical features of the disease may be progressive, especially in older adulthood. The X-linked form may be associated with visual acuities ranging from 20/25 to 20/400. Diagnosis is usually based on an electroretinogram.

Stargardt Disease and Fundus Flavimaculatus

Degenerative genetic disorders affecting primarily the central retina are referred to as macular dystrophies. These diseases are rare, with an estimated prevalence of 1:10,000. The most common form is Stargardt disease, which is usually transmitted as an autosomal recessive disorder. Autosomal dominant transmission may also occur. The gene that, when mutated, most often causes autosomal recessive Stargardt disease is ABCA4 (ATP-binding cassette, subfamily A, member 4). Fundus flavimaculatus is an allelic subtype of Stargardt disease that has been associated with mutations in the ABCA4 and PRPH2 genes.

The disease is characterized by a bilateral, relatively symmetric, progressive loss of central visual acuity, usually occurring between the ages of 6 and 20 years. Generally, the reduced vision antedates and is out of proportion to the initial ophthalmoscopic changes. Progressive atrophy of the macula is heralded by loss of the normal macular reflex and development of a “beaten bronze” appearance. Multiple pisciform (fish-shaped), yellowish subretinal flecks usually develop in the macular region (Fig. 582-3) and, in the variant fundus flavimaculatus, throughout the retina. Vision often decreases to legal blindness, which is 20/200 or less. Total loss of vision is rare, and night blindness (nyctalopia) is not a characteristic feature. The electroretinogram is typically normal but may be variably depressed. A dark choroid (hypofluorescence caused by the blockage of the normal choroidal fluorescence) may be noted on fluorescein angiography and is helpful diagnostically. This sign is not seen in other genetic retinal diseases that have subretinal flecks such as fundus albipunctatus, retinitis punctata albescens, Kandori fleck retina, and vitamin A deficiency.

Cone Dystrophy

In contrast to classic retinitis pigmentosa, cone dystrophy is usually characterized by reduced central visual acuity, initially without changes in the rod system. The mode of inheritance may be autosomal dominant, autosomal recessive, or X-linked recessive. Complaints of poor visual acuity, poor color vision, and photophobia (sensitivity to light) usually occur late in childhood or early adulthood. Ophthalmoscopic findings of the macula are variable and may include a normal appearance, a mottled pattern, “bull’s-eye” atrophy (ringlike pigmentary changes around the foveal area), or localized atrophy. The electroretinogram shows a normal scotopic (dark-adapted, rod) response but an absent or severely depressed photopic (light-adapted, cone) response. Over time, rod involvement may lead to a diagnosis of cone-rod dystrophy. Relief of photophobia may be achieved by using Corning sunglasses or colored contact lenses.

If the rods eventually become involved, the disorder is termed a cone-rod dystrophy. There are autosomal recessive, autosomal dominant, and X-linked recessive forms of this condition.

Achromatopsia

Achromatopsia, also known as rod monochromatism, is a rare (3 in 100,000) autosomal recessive condition characterized by severe color blindness and photophobia with markedly decreased vision due to dysfunction of cone cells in the retina. Symptoms usually become apparent in infancy with the development of nystagmus. Vision is better in dim illumination. The condition is generally not progressive, and there are no associated neurologic abnormalities. The fundus is typically normal in appearance but may include an abnormality, or the absence, of the foveal light reflex. The cone electroretinogram is markedly abnormal, whereas the rod waveforms are normal. At least 3 genes that play essential roles in the cone phototransduction cascade are known to be involved, and 2 of the 3 genes (CNGA3, CNGB3) encode the α- and β-subunits of the cyclic nucleotide guanosine monophosphate (GMP)-gated channel located in the outer membrane of the cone outer segments. Mutations in these genes account for about 97% of achromatopsia cases. The third gene, GNAT2, encodes the guanine nucleotide–binding protein, α-transducin activity polypeptide 2, responsible for 2% to 3% of achromatopsia cases. In addition, mutations in at least 3 other genes (PDE6C, PDE6H, ATF6) have been reported to cause total achromatopsia.

Bestrophinopathies

Bestrophinopathies include Best vitelliform macular dystrophy (BVMD, Best disease), autosomal dominant vitreoretinochoroidopathy (ADVIRC), and autosomal recessive bestrophinopathy (ARB). Best disease is the most common. It is an autosomal dominant disorder of the macula. Variable penetrance and expressivity are common. Onset is usually during childhood years, and several stages in the clinical evolution of disease have been identified. In the early stage, Best disease is usually characterized by bilateral, symmetric, well-defined, round “egg yolk” (vitelliform) lesions in the maculae (Fig. 582-4). In most cases, visual acuity is initially good despite the distinctly abnormal retinal appearance. An atypical form with multifocal vitelliform lesions may occur. The homogeneous, yellow appearance of the macular lesions may “layer out” and fragment with time, ultimately leaving a mottled scrambled egg appearance that may simulate other types of macular degeneration. Although there usually is loss of visual acuity, the long-term visual prognosis is good, with 20/40 vision in at least 1 eye through age 50 years. The electroretinogram is normal, but the electro-oculogram is abnormal and confirms the diagnosis. Some affected individuals are clinically unaffected but also have an abnormal electro-oculogram. The abnormal gene (VMD2) produces the protein bestrophin 1, a transmembrane protein of the retinal pigment epithelium involved in chloride transport.

Leber Congenital Amaurosis

This retinal dystrophy presents early in infancy with nystagmus and is responsible for an estimated 10% to 18% of all infantile visual impairment. Visual acuity ranges from 20/80 to no perception of light. Other features include high hyperopia (farsightedness), keratoconus, and, rarely, cataracts. Oculodigital phenomenon (eg, self-stimulation by digital poking of the eye) is common. The fundus presentation varies from a normal appearance to macular coloboma (similar in appearance to a toxoplasmosis scar) or classic retinal degenerative changes of retinitis pigmentosa (see above). The clinical presentation may include a multisystem disease with associated neurologic findings, including progressive loss of milestones and renal abnormalities. The electroretinogram is nonrecordable early in life and is essential for the diagnosis.

Leber congenital amaurosis usually is inherited in an autosomal recessive pattern. Mutations of multiple genes, which disrupt several key retinal pathways, have been identified (www.sph.uth.tmc.edu/RetNet/). Studies of gene therapy in the forms caused by mutations of RPE65 (retinal pigment epithelium-specific protein, 65 kD) have been initiated in humans with some remarkable success in children.

Intrauterine/Infantile Retinal Detachment and Retinal Dysplasia

Norrie Disease

Norrie disease is a rare, X-linked recessive disease that affects only males. Female carriers may show mild peripheral retinal failure of vascularization. Intrauterine or infantile bilateral retinal nonattachment, sometimes described by the term retinal dysplasia, is usually identified by the presence of leukocoria (white pupil) or nystagmus. Over time, corneal opacities or cataract develop, and the eyes atrophy (phthisis). Delayed development and sensorineural deafness also develop. The Norrie disease gene (NDP) encodes the protein norrin.

Familial Exudative Vitreoretinopathy (Familial Vitreoretinal Dysplasia)

Familial exudative vitreoretinopathy (FEVR) is similar to Norrie disease but is not associated with deafness or delayed development. X-linked recessive, autosomal dominant, or autosomal recessive patterns of inheritance have been documented. Typically, the affected infant has bilateral visual impairment with nystagmus. Abnormalities of the temporal retina or incomplete retinal vascularization may result in dragging of the retina and subsequent retinal detachment. Mutations in NDP also may cause the clinical features of X-linked FEVR. An autosomal dominant form may be caused by mutations of the frizzled-4 gene (FZD4), a transmembrane receptor. Both autosomal recessive and dominant forms may be caused by mutations of the low-density lipoprotein receptor-related protein 5 (LRP5), a cell surface protein.

Retinal dysplasia may occur as an isolated ocular disorder or may be associated with chromosomal anomalies such as trisomy 13 or single-gene multisystem disorders such as Meckel syndrome. The dysplastic retina results in nonattachment during embryogenesis and a very poor visual prognosis.

Vitreoretinal Diseases

Juvenile Retinoschisis

X-linked juvenile retinoschisis is one of the most common reasons for unexplained visual loss in young male patients. This X-linked recessive disorder is characterized by a bilateral schisis (splitting) within the nerve fiber layer of the retina. Initially, vision may be reduced only mildly, but it can decrease gradually with age, ending in the 20/200 range or worse. The initial appearance of the foveal region is that of characteristic, radiating striae in the nerve fiber layer. With time, the macula becomes mottled and atrophic. In more than half of affected patients, the macular changes are the sole ophthalmoscopic finding. Schisis of the peripheral regions of the retina also may be evident. Vitreous hemorrhage resulting from torn retinal vessels bridging the area of schisis or retinal detachment with sudden deterioration of vision may complicate this disorder. The electroretinogram may be helpful in confirming the diagnosis. Juvenile retinoschisis is caused by mutations in the retinoschisin 1 (RS1) gene.

Stickler Syndrome

Stickler syndrome is an autosomal dominant, and rarely autosomal recessive, disease with variable penetrance and expressivity. The ocular findings may include high myopia, cataract, vitreoretinal degeneration, perivascular pigmentary retinopathy, and retinal detachment. Systemic features include progressive arthropathy, epiphyseal dysplasia, characteristic facies, and cleft palate. Some patients have the Pierre Robin sequence. Because of the subtle, yet extensive, nature of the nonocular features of the syndrome, early diagnosis of the disease may depend on an eye evaluation. Patients with cleft palate, especially when they have or there is a family history of myopia, deserve an eye examination. Early diagnosis is critical because of the risk of peripheral vitreoretinal pathology and retinal detachment.

The primarily ocular form is caused by mutations of the collagen, type II, alpha-1 gene (COL2A1). The multisystem forms include different bone diseases and may be caused by mutations in 1 of several collagen genes, including the collagen, type XI, alpha-2 (COL11A2); the collagen, type XI, alpha-1 (COL11A1); and COL2A1 genes. An autosomal recessive form of the disease is caused by mutations of the collagen, type IX, alpha-1 and alpha-2 (COL9A1, COL9A2) genes.

MITOCHONDRIAL DISORDERS

Mitochondrial deletions may be associated with external ophthalmoplegia (progressive loss of eye movement) and a pigmentary retinopathy that may be similar to retinitis pigmentosa. The Kearns-Sayre syndrome is a specific form of the disease and consists of the triad of a pigmentary retinopathy, progressive external ophthalmoplegia, and cardiac arrhythmias. Onset of symptoms may occur in the first decade of life. The external ophthalmoplegia usually includes ptosis. Diplopia is uncommon. The pigmentary retinopathy may have little effect on the central vision and visual fields. The arteriolar attenuation and pallor of the optic nerve, commonly associated with retinitis pigmentosa, may be absent. Systemic findings include muscle weakness, ataxia, hearing loss, and dementia. An electrocardiogram is important in all cases of acquired ophthalmoplegia of unknown etiology.

Mitochondrial dysfunction can result from mutations in nuclear autosomal genes, the products of which are expressed in the mitochondria. The nuclear-encoded DNA polymerase-gamma (POLG) gene, if mutated, may cause autosomal recessive or autosomal dominant disease. Other nuclear genes that can predispose an individual to autosomal dominant mitochondrial deletions include the ADP/ATP translocator or adenine nucleotide translocator (ANT; solute carrier family 25, member 4 [SLC25A4)]), the twinkle protein (C10ORF2), and the nuclear-encoded DNA polymerase gamma-2 (POLG2) genes.

Leber hereditary optic neuropathy (LHON) was the first disorder recognized to be of mitochondrial etiology. The incidence ranges from 1:25,000 to 1:40,000. Typically, sudden visual loss occurs in the third decade but can occur as early as age 1 year and as late as the ninth decade. Although visual loss ranges from 20/50 to no light perception, it is typically profoundly reduced. Spontaneous recovery may occur. Early in the disease, optic nerve edema and circumpapillary vessel dilation occur. Eventually, optic nerve pallor develops. The disease is a bilateral condition but is usually asynchronous in presentation. Recovery of some vision can occur. The disease occurs predominantly in Caucasians, and unlike other mitochondrial disorders, which affect both genders equally, males are more likely and more severely affected. The reason for the male preponderance is unknown. Both genetic and environmental modifiers have been proposed. Evidence suggests that cigarette smoking and alcohol consumption may worsen the prognosis. Over 90% of affected individuals have mutations at base pairs 11778, 3460, and 14484, with visual outcome the best with the 14484 mutation. The MITOMAP Web site (http://www.mitomap.org) is a human mitochondrial genome database that contains a compendium of polymorphisms and mutations of the human mitochondrial DNA. It gives an up-to-date overview of confirmed and possible LHON mutations.

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CONGENITAL ANOMALIES

Optic Nerve Hypoplasia

Optic nerve hypoplasia is the most common congenital disc anomaly observed in the pediatric ophthalmology setting. It is an outcome of errors in early intrauterine fetal development, in which abnormal pruning and/or migration of retinal ganglion axons result in a reduction in the total number of axons within the optic nerve. Fundus exam can vary but typically demonstrates a small optic disc with either normal pigmentation, grayish or pale color. The disc is often surrounded by a white or yellow peripapillary halo, which is surrounded by a second ring of pigment (double ring sign) corresponding to the size of a normal disc (Fig. 583-1). The disc may appear normal in structure with intact cup and neuroretinal rim or can appear anomalous with sectoral loss (eg, superior segmental optic nerve hypoplasia). The distance from a normal temporal disc edge to the macula is 3 disc diameters. If the optic nerve is small, the number of disc diameters increases to greater than 3.5 disc diameters. The retinal vasculature may be tortuous and/or angulated, and the optic cup may be underdeveloped. Neuroimaging often misses mild optic nerve hypoplasia. Moderate to severe optic nerve thinning suggestive of optic nerve hypoplasia can be seen, but clinical exam is needed to confirm and distinguish this from optic nerve atrophy. The diagnosis on clinical exam can be difficult if the hypoplasia is mild; disc photography and quantitative assessment of optic nerve head by optical coherence tomography (OCT) may be helpful in establishing a diagnosis.

The visual acuity of an affected eye can range from normal to no light perception. The size or appearance of the optic disc does not predict the vision potential or the perseveration of an intact and functional papillomacular bundle. Optic nerve hypoplasia has been associated with fetal alcohol syndrome, maternal diabetes (usually a hemihypoplasia affecting the upper or lower half of the disc), in utero cytomegalovirus infection, toxemia, adolescent pregnancy, and maternal use of quinine, anticonvulsants, aminopterin, or illicit drugs. Accompanying ocular disorders may include aniridia, albinism, coloboma, Duane retraction syndrome, and high myopia.

Optic nerve hypoplasia can be unilateral and bilateral. With bilateral involvement, 75% of individuals have accompanying neurodevelopmental problems. In bilateral optic nerve hypoplasia, particularly in severe forms, patients may have poor vision and nystagmus early in life, as well as associated abnormalities such as mental retardation, delayed development, seizures, deafness, cerebral atrophy, hemiparesis, ventricular defects, porencephalic cyst, hypopituitarism, hypothyroidism, and diabetes insipidus. Sudden death has been reported in response to a viral illness likely due to unrecognized pituitary insufficiency. Septo-optic dysplasia, also known as de Morsier syndrome, is characterized by the constellation of findings including (1) optic nerve hypoplasia; (2) midline central nervous system abnormalities such as hypothalamic dysfunction, pituitary dysfunction, and malformation of the optic chiasm; and (3) agenesis of the septum pellucidum or corpus callosum. Patients have characteristic facies with a broad forehead and large anterior fontanelle.

In unilateral optic nerve hypoplasia, 20% of affected individuals have serious central nervous system abnormalities. Patients with unilateral optic nerve hypoplasia are typically identified due to decreased vision and strabismus, with initial presentation commonly found later in preschool age from failed vision screening. Children with unilateral optic nerve hypoplasia and asymmetric bilateral optic nerve hypoplasia can develop amblyopia in addition to the organic visual loss and should be treated with patching of the sound eye for optimal visual development. If hypoplasia is unilateral or asymmetric, there may be an afferent pupillary defect (Marcus Gunn pupil); however, color vision is remarkably spared.

Given the high incidence of associated central nervous system anomalies and endocrinologic problems, all patients with optic nerve hypoplasia (unilateral or bilateral) need a complete endocrine and neurological workup, including neuroimaging. Characteristic magnetic resonance imaging (MRI) findings include absent infundibulum of the pituitary or ectopic posterior pituitary bright spot. Even if no structural abnormalities are found on neuroimaging, the hypothalamus-pituitary axis may be hypofunctioning. All affected children require an initial endocrine evaluation evaluating for hypopituitarism. Patients with partial absence of the septum pellucidum have a 3-fold lower risk of pituitary hormone deficiency than those with complete absence of the septum pellucidum. Early recognition and treatment of hormone imbalance help the affected child achieve normal growth and development.

Coloboma

The colobomatous optic nerve appears as an enlarged, white, excavated nerve head with or without extension of the surrounding retina and choroid (Fig. 583-2). Optic disc coloboma can be unilateral or bilateral, and occurs sporadically. Optic nerve coloboma is due to incomplete closure of the posterior end of the embryonic fissure of the optic cup in the seventh week of gestation, resulting in the development of an inferiorly decentered, enlarged, bowl-shaped, excavated optic disc. The incomplete closure of the fissure can affect the iris and inferior choroid and retina, which can be found in association with optic disc coloboma or as isolated findings. Microphthalmia may be present. Neuroimaging can also demonstrate a large crater-like excavation at the optic nerve head. Visual potential is dependent on the integrity of the papillomacular bundle. If the optic nerve coloboma is large, subarachnoid cerebrospinal fluid around the optic nerve may flow through the defect under the retina producing a serous detachment of the retina and interfering with macular function. Serous detachments can be managed by observation, patching, corticosteroids, vitrectomy with gas-fluid exchange, and photocoagulation. Given the possibility of late retinal detachment, patients should be followed at least annually. Optic nerve colobomas can be associated with multiple systemic dysmorphsims in conditions such as CHARGE syndrome, Aicardi syndrome, and Goldenhar sequence. Several genes, including PAX6, CHX10, SOX2, and CHD7, have been implicated in this process.

MORNING GLORY DISC ANOMALY

Morning glory optic disc anomaly is a congenital, posterior fundus excavation that involves the optic nerve. The disc appearance resembles the morning glory flower. Most instances are unilateral and nonfamilial. The optic nerve is located in the center of an enlarged, excavated disc with central fibroglial tissue (Fig. 583-3). It can be orange or pink in color, with anomalous retinal vessels splayed radially out at the periphery of the disc. There are peripapillary pigmentary chorioretinal changes and small arteriovenous communications that surround the optic disc. It is twice as common in females as in males and rare in African Americans. Visual acuity is usually 20/200 or worse, although it is difficult to predict the visual potential based on the appearance of the anomaly. There are a few cases of vision as good as 20/20. Given the unilateral presentation, patching the unaffected eye may be helpful in preventing and reversing amblyopia, which may contribute to vision loss. Later sequelae include high myopia and visual field defects. Serous retinal detachment is the most serious ocular complication and may occur in up to 26% to 38% of patients. Subretinal leakage around the nerve, potentially from neovascularization, is the hypothesized source for the subretinal fluid. Although usually isolated, association with sphenoidal encephalocele is known and may be suspected if the patient also has a notch in the center of the lip. Morning glory optic nerve has also been reported in trisomy 4q and the PHACE syndrome (posterior fossa malformations; hemangiomas; arterial abnormalities; cardiac defects, especially aortic coarctation; and eye abnormalities). Moyamoya disease is another well-known associated condition.

Optic Nerve Pit

Optic nerve pits are characterized by dark gray oval or slitlike holes in the disc, usually on the inferotemporal side, but can involve any quadrant of the disc. They are usually unilateral, but up to 15% can be bilateral, and they most often have no hereditary pattern. In unilateral involvement, the disc is slightly larger and there are peripapillary changes adjacent to the location of the pit.

Visual acuity is typically normal, especially in the absence of subretinal fluid, but visual field defects can vary with regard to the location of the optic nerve pit. The most common visual field defect is an enlarged blind spot. Optic pits are important clinically, because they may produce scotomas, at times associated with serous retinal detachments. Retinal detachments have been observed in children as early as the first decade. Attempts to repair the elevated retina with silicone oil injected into the eye can be complicated by silicone oil migrating into the subarachnoid space of the optic nerve. Systemic abnormalities are not commonly associated with congenital optic nerve pits.

Myelinated Nerve Fibers

In normal development, myelination of the optic nerve usually ceases at the lamina cribrosa prior to birth. Occasionally, it proceeds distally, extending intraocularly to produce a congenital, white, feathery opacification of the neuroretinal rim and peripapillary retina (Fig. 583-4). Visual acuity is usually unaffected unless the myelination extends into the fovea; however, visual field scotoma is commonly noted, and the blind spot may be enlarged. This condition is bilateral in 20% of patients. Extensive myelinated nerve fibers have been associated with high myopia and amblyopia, classically resistant to treatment.

Persistent Fetal Vasculature

A persistence of the primary vitreous, previously referred to as persistent hyperplastic primary vitreous (PHPV), has been renamed persistent fetal vasculature (PFV). The hyaloid artery and vein normally course from the optic disc to the back of the lens in utero and spontaneously reabsorb in the third trimester. At the back of the lens, the hyaloid system is confluent with a dense array of vasculature that envelops the lens, including the tunica vasculosa lentis on the lens surface, and communicates with iris vessels. In PFV, there is failure of regression of this vasculature to varying degrees. The manifestations of PFV include abnormalities of pupil size and iris development, which are usually visually insignificant but can appear as a dense cataract with extensive retrolental fibrovascular tissue between the optic nerve and posterior lens. The lens posterior capsule is abnormally vascularized and fibrotic. This may cause the ciliary processes to be pulled in centrally with anterior displacement of the iris-lens diaphragm. Angle-closure glaucoma may result. Occasionally the retina may also be involved. Microphthalmia is common. Visual prognosis is guarded, but satisfactory results can be obtained if the macula is not involved and if cataract surgery is performed early in infancy, followed by aggressive patching of the unaffected eye. The disorder is almost always unilateral, isolated, and sporadic.

Optic Nerve Drusen

Intrapapillary drusen or hyaline bodies of the optic nerve head are tiny white or yellow translucent masses of hyaline-like material buried within the substance of the optic nerve head anterior to the lamina cribrosa. They occur almost exclusively in whites, with an incidence of 0.3% to 1.0% clinically and 2% histopathologically. They are bilateral in 75% to 80% of cases. In young children, the masses are inconspicuous, but within 1 to 2 decades, they become visible on the surface of the disc as shiny, refractile bodies that glow with indirect light. They may elevate the nerve head, thus simulating papilledema (pseudopapilledema). Drusen of the optic disc can be identified in at least 75% of the instances of pseudopapilledema. Pseudopapilledema and neurologic disorders that frequently coexist by coincidence (eg, headache) may lead to unnecessary neuroradiologic and neurosurgical investigations for exclusion of an intracranial process. Because drusen of the optic nerve can be inherited as an autosomal dominant trait, ophthalmoscopic examination of family members may disclose similar lesions and thus help establish the correct diagnosis in a child with pseudopapilledema. Ophthalmoscopy is diagnostic if the drusen are visible. Ultrasonography and OCT may be helpful ancillary tests if the drusen are buried. Visual acuity is usually unaffected in 85% to 90% of patients, although visual field defects have been reported in 10% to 15%. Rarely, subretinal neovascular membranes with hemorrhage may compromise central acuity.

OPTIC DISC EDEMA

Optic disc edema has a variety of potential etiologies including inflammatory, vascular, infectious, traumatic, and compressive. In each of these cases, the inciting factor results in blockage of axoplasmic flow of the retinal ganglion cell axons that make up the nerve. Optic nerve edema is characterized by various stages of elevation and congestion of the optic nerve head, blurring of the disc margin, obliteration of the physiologic cup, venous congestion, loss of spontaneous venous pulsations, peripapillary splinter hemorrhages, and edema of the peripapillary retina (Fig. 583-5). Several conditions can mask optic nerve edema including high myopia (5–10 diopters), high hyperopia, optic nerve drusen, and anomalous optic nerve (commonly seen in trisomy 21).

In the early stages of optic nerve edema, visual acuity, color vision, and pupillary responses may not be affected. With ongoing or chronic optic nerve edema, retinal ganglion cells gradually die and the optic nerve becomes progressively pale and atrophic. With chronic optic nerve edema, progressive visual field defects and ultimately decreased central visual acuity ultimately occur. The hallmarks of chronic papilledema include optic atrophy, pallor, and poor central visual acuity.

Idiopathic Intracranial Hypertension

Idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, is characterized by papilledema (optic nerve edema with elevated intracranial pressure), normal cerebrospinal fluid composition, and normal neuroimaging with absence of an intracranial mass. Common symptoms and signs of IIH include headache, pulsatile tinnitus, transient visual obscurations, diplopia, and neck pain (especially with children). After computed tomography (CT) or MRI to rule out intracranial pathology, a spinal tap may reveal an opening pressure of greater than 28 to 30 cm H₂O. In postpubescent children and adults, IIH is more common among obese young women. However, in prepubescence, IIH can more commonly affect boys with a high incidence of endocrine abnormalities. Primary IIH is an idiopathic disease with association to body weight and can be effectively treated with weight control. Secondary IIH occur with steroid withdrawal, vitamin A intoxication, fluoroquinolone and tetracycline drug ingestion, growth hormone, all-trans-retinoic acid (tretinoin), head trauma or surgery, dural sinus thrombosis, hyperviscosity syndromes, and systemic lupus erythematosus. In any etiology, the goal of treatment is to reduce intracranial pressure and prevent permanent visual loss. Treatment may include serial lumbar punctures, diuretics, optic nerve sheath fenestration, lumboperitoneal and ventriculoperitoneal shunt procedures, and weight reduction for obese patients. Medications associated with the development of IIH should be discontinued. Papilledema that is severe and chronic can result in irreversible vision loss, even after adequate control of the intracranial pressure.

Optic Neuritis

Optic neuritis refers to inflammation of the optic nerve. Inflammation of the nerve posterior to the globe is called retrobulbar optic neuritis. Optic neuritis is characterized by profound loss of visual acuity within hours or days, pain with eye movement, the development of a central scotoma visual defect, depressed color vision, and an afferent pupillary defect (Marcus Gunn pupil) in the affected eye. Worsening of vision with exercise or other increase in body temperature has been referred to as Uhthoff phenomenon and is more frequent in systemic demyelinating disease.

There are clear differences in adult and pediatric optic neuritis. Children with optic neuritis more commonly present with bilateral involvement, anterior optic nerve edema, and association with postviral infection. Adult optic neuritis commonly presents as unilateral involvement, retrobulbar inflammation of the nerve, and association with demyelinating disease.

Pediatric optic neuritis may result from inflammation of contiguous structures or from systemic infection. Optic neuritis secondary to meningoencephalitis is not uncommon. The optic nerves can be involved by spread from orbital abscesses, cellulitis, and foci of infection in the teeth, tonsils, or sinuses. Optic neuritis can develop in the setting of infectious viral diseases such as measles, mumps, varicella, poliomyelitis, mononucleosis, and influenza. It has also been reported following vaccination for viral diseases. Optic neuritis usually appears 1 to 2 weeks after the onset of an infectious illness and resolves completely. Even with apparently full recovery, pallor of the disc and nerve fiber layer defects are signs of prior optic nerve dysfunction. Marked loss of vision occasionally results, with partial or complete atrophy of the nerve. Optic neuritis may also occur with syphilis, Guillain-Barré syndrome, Behçet disease, various leukodystrophies, Schilder disease, and neuromyelitis optica.

Optic neuritis is less commonly associated with multiple sclerosis (MS) in children than adults. Longitudinal studies in adults have shown a clear association between optic neuritis and MS. The majority of women who have a single episode of optic neuritis go on to develop demyelinating disease like MS. The conversion rate for men is slightly lower. In contrast, anterior optic nerve edema and retrobulbar optic neuritis in childhood appear to be self-limited with little risk for subsequent central nervous system involvement.

The Optic Neuritis Treatment Trial study in adults found that intravenous methylprednisolone (1 g/d for 3 days) followed by oral prednisone (1 mg/kg/d for 11 days) hastened the rate of visual recovery from optic neuritis in adults but did not affect final visual outcome. Treatment with oral prednisone alone was no better than placebo. Intravenous methylprednisolone treatment also reduced the 2-year incidence of definite MS (a new neurologic deficit occurring at least 4 weeks after the onset of optic neuritis) by more than 50%. These data have been generalized to pediatric patients, with most pediatric neurologists and neuro-ophthalmologists electing to treat children with idiopathic optic neuritis using similar protocols.

TUMORS OF THE OPTIC NERVE

Tumors involving the optic nerve may produce proptosis and progressive vision loss. Strabismus and an afferent pupillary defect (Marcus Gunn pupil) may also occur.

Optic Nerve Glioma

Optic nerve glioma is the fourth most common orbital tumor of childhood and is the most common tumor of the optic nerve in childhood. Ninety percent of optic gliomas are seen by the end of the second decade of life. The peak incidence is between age 2 and 6 years; 75% become apparent before age 10. Between 25% and 50% of patients have neurofibromatosis, and 15% to 25% of patients with neurofibromatosis type 1 (NF-1) have optic nerve gliomas.

Optic nerve gliomas may arise anywhere along the optic nerve, including the chiasm. Gliomas anterior to the chiasm behave in a benign fashion, whereas those in and posterior to the chiasm may be more aggressive. When the tumor arises in the orbit, ophthalmoscopic findings may include optic disc edema, optic atrophy, and retinal striae from pressure by the tumor on the posterior surface of the globe. Optociliary shunt vessels (vessels that shunt blood from the retinal to the choroidal venous circulation) may be seen on the surface of the optic nerve head. Chiasmal gliomas cause bilateral vision loss and optic atrophy without proptosis. An afferent pupillary defect may develop if one optic nerve is compressed more than the other. If a chiasmal glioma enlarges sufficiently, endocrine dysfunction may ensue from mass effect on the pituitary gland and hypothalamus. Hydrocephalus, head nodding, and nystagmus (often asymmetric) may develop as a result of compression of the third ventricle. The diagnosis of optic nerve glioma is made by the clinical findings and by neuroimaging. Orbital tumors produce a fusiform enlargement of the optic nerve. Enlargement of the optic foramen and sella turcica have also been observed. Histopathologically, optic nerve gliomas are pilocytic astrocytomas of the juvenile type.

Treatment is predominantly based on characterization of the optic nerve glioma. NF-1–associated optic nerve gliomas are benign hamartomas that grow slowly, and the majority of patients have a paucity of symptoms and signs. There are even reports of spontaneous involution. NF-1–associated optic nerve gliomas are typically monitored closely until the age of 7 to 8, and then can be followed annually as the chances of growth are low after this age. Those that grow to compromise optic nerve function can be treated effectively with chemotherapy. Optic nerve gliomas that are not associated with NF-1 can be quite aggressive, especially when present early in life. If there is minimal visual loss without proptosis, the child may be kept under observation. If there is progressive loss of vision with little or no proptosis, aggressive chemotherapy and radiotherapy are considered to stabilize growth of the tumor and normalize the vision. Surgical excision is probably not indicated unless disfiguring proptosis develops or there is extension toward the chiasm. For chiasmal gliomas, surgery is not advised; radiotherapy seems to be the best method of treatment.

Optic Nerve Meningioma

Optic nerve meningioma is seen more often in adulthood, is 5 times more common in females than males, and is rare in childhood. However, when present, it can be aggressive. Presenting signs, symptoms, and ophthalmoscopic findings are the same as for optic nerve glioma. This tumor is also associated with neurofibromatosis. The compressive optic neuropathy produced by optic nerve meningioma may result in blindness, optic atrophy, and the formation of optociliary shunt vessels. Imaging studies may demonstrate a discrete mass or diffuse thickening of the optic nerve. Following contrast injection, the periphery of the nerve enhances, the so-called railroad or “tram” track sign. Histopathologically, optic nerve meningiomas arise from arachnoid meningoendothelial cells. Treatment is surgical debulking followed by chemotherapy and radiation.

OPTIC ATROPHY

Optic atrophy is the ultimate result of optic nerve injury, regardless of cause. It is characterized by ganglion cell and axon loss, nerve head pallor (Fig. 583-6), reduced visual acuity, scotoma, poor color vision, and the development of an afferent pupillary defect (Marcus Gunn pupil) in the affected eye. The optic nerve head of the normal, healthy infant can be paler than that of the adult; therefore, a diagnosis of optic atrophy in the infant should be made only when one is sure of the findings. Attention to the normally prominent macular nerve fiber layer of the retina in children may be helpful in recognizing when there is a reduction in the number of nerve fibers. Optic nerve hypoplasia and other congenital disc anomalies are much more common than optic atrophy in the first year of life.

When optic atrophy in a child presents a diagnostic dilemma, the investigation should include detailed family history, search for metabolic or toxic factors, careful eye examination, evaluation for vasculitis or infection, imaging studies of the skull, orbits, and optic foramina, and consideration of other ancillary tests such as neuroimaging, OCT, electrophysiology, and genetic testing. A useful clinical pearl is that children blind from retinal disorders are more likely to rub their eyes (oculodigital phenomena) than children blind from disorders of the optic nerve or cortex. Also, they may exhibit a paradoxical response to optokinetic nystagmus drum testing.

Autosomal Dominant Hereditary Optic Atrophy

Autosomal dominant optic atrophy (Kjer optic atrophy) is the most common form of hereditary optic atrophy. Mild to moderate reduction in vision with no nystagmus becomes apparent between 4 and 8 years of age. Bilateral vision loss may be slowly progressive throughout life. A scotoma with impaired color vision and normal electroretinogram (ERG) are characteristic. Temporal atrophy of the optic nerve is most prominent. The genetic defect has been linked to 3q28-q29 and 18q12.2-12.3. In the former, mutations in the OPA1 gene Msp1, which encodes for the GTPase protein dynamin, are known to be causative.

Other Inherited Optic Atrophies

Optic atrophy may be seen in inherited neurologic diseases that include Canavan disease, Charcot-Marie-Tooth disease, infantile subacute necrotizing encephalomyelopathy, Friedreich ataxia, and familial dysautonomia. These diseases are autosomal recessive, with Charcot-Marie-Tooth disease inherited also as an X-linked recessive disorder. Isolated autosomal recessive optic atrophy has been linked to 8q21-22 with another variant due to mutations in the 3-methylglutaconic aciduria III gene at 19q13.2-13.3. Leber optic atrophy is discussed in Chapter 582.

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