Neonatal Eyelid, Orbit, and Lacrimal Disorders: A Clinical Overview

After completing this article, readers should be able to:

1. Identify eyelid anomalies in the neonate, especially those that can lead to corneal exposure and visual compromise.

2. Identify when orbital anomalies in the neonate can affect vision and how orbital findings can help in the clinical diagnosis of systemic syndromes.

3. Describe the initial steps of diagnosis and treatment of lacrimal disease in the neonate. 

The periocular adnexa comprises the eyelids, the contents of the orbit (including the orbital bones, extraocular muscles, nerves, and vessels), the lacrimal gland, and the drainage system. These structures protect the eyeball and the optic nerve.

Disorders resulting in abnormalities, absence, or malfunction of the periocular adnexa may be visually significant due to resulting ocular surface exposure, strabismus, or amblyopia. In this review, we will describe the disorders of the eyelids, orbits and tear ducts that can occur in the newborn and that justify early recognition by doctors to avoid possible consequences. 

The eyelids are composed of 7 structural layers that include the skin, the protraction muscle (orbicularis oculi), the orbital septum, the orbital fat, the retraction muscles (levator palpebrae superioris, Müller’s muscle), the tarsus and the conjunctiva.1

The primary function of the eyelid is to lubricate and protect the ocular surface.

Congenital eyelid anomalies occur during pregnancy due to developmental arrest or failure of fusion. 1 Malfunctioning eyelids can leave the ocular surface vulnerable to exposure and dryness, which, in turn, can cause visually significant corneal abrasions and scars. Furthermore, if the position of the eyelids is abnormal, the neonate’s vision may be affected by visual deprivation or by refractive error and consequent amblyopia.

>> Eyelid malformation 

> Cryptophthalmos. Cryptophthalmos is a rare birth defect in which the eyelids do not separate in utero; It is characterized by a sheet of skin that runs from the forehead to the cheek over a malformed globe. It may be complete, in which there are no identifiable ocular adnexal structures, and ultrasound only shows a vestigial ocular structure or a cyst where the globe should be. In incomplete cryptophthalmos, the malformed upper eyelid is fused to the globe with a keratinized cornea. 1,2 The structural layers of the affected eyelid, such as the orbicularis, septum, levator, and tarsus, are also often malformed. Since the underlying globe is usually quite malformed and the visual potential of the affected side is very limited, reconstructive surgery may be delayed as the child matures to allow growth and relaxation of the affected tissues. 3, 4 However, in cases with bilateral involvement, where the underlying globe holds promise for potential visual potential, or where there is a risk of severe corneal exposure, a more urgent reconstruction may be warranted. 3 

> Ankyloblepharon. Ankyloblepharon is characterized by the adhesion of the upper and lower eyelids to each other. It may be partial (ankyloblepharon filiform adnatum) or complete, depending on the amount of palpebral fissure fused. 1, 3 During pregnancy, the margins of the eyelids remain fused until the end of the fifth month, when separation begins, with the eyelids reaching complete separation in the seventh month. 3, 5 When ankyloblepharon is present, additional systemic evaluation is warranted, given its association with cleft lip and palate, as well as syndactyly. 6,7 Importantly, the structures of the eyelid and underlying globe are normal; therefore, the eyelids can be opened at the fusion line with ophthalmic scissors or a scalpel. 3 

>Euriblepharon. Euryblepharon refers to a congenital enlargement of the horizontal palpebral fissure and shortening of the vertical palpebral fissure with lateral and downward displacement of the lateral canthus1 It may be inherited as an autosomal dominant disorder or occur sporadically; It is also seen in various systemic conditions such as Kabuki syndrome and trisomy 21. Euiblepharon can cause incomplete blinking and lagophthalmos (incomplete eyelid closure). Depending on the severity of the corneal exposure, mild cases may be treated with lubrication using artificial tear drops and gel ointments, while more severe cases require surgical reconstruction in the form of lateral canthal repositioning.1  

> Coloboma of the eyelid. A coloboma is an embryological cleft that causes the absence of tissue. To be considered a true eyelid coloboma, the eyelid margin must also be involved. 1, 3 Upper eyelid colobomas are frequently associated with Goldenhar syndrome (also called "oculoauriculovertebral dysplasia"), which also includes mandibular hypoplasia, ear anomalies such as microtia and/or preauricular skin tags, limbal dermoid cysts, and vertebral anomalies1, 8 Colobomas of the lower eyelid have been described in Treacher Collins syndrome; however, some refer to this as a pseudocoloboma, as there is a defect typically of subcutaneous tissue alone.1 The timing of eyelid coloboma repair depends on the degree of exposure of the cornea, like other eyelid malformations before mentioned. If corneal exposure is well controlled with lubrication, surgery can be delayed, allowing tissue growth and relaxation. 

> Malposition of the eyelid 

>> Congenital Ectropion

Ectropion is defined as an outward rotation of the eyelid margin, most commonly the lower eyelid. Congenital ectropion usually occurs due to a deficiency in the anterior lamella of the eyelid (defined as the skin and orbicular layers) and is often associated with blepharophimosis ptosis epicanthus inversus syndrome (BPES), trisomy 21, or ichthyosis.1 As a result, The lower ocular surface that is usually protected by the eyelid may be exposed and prone to dryness. Additionally, ectropion can cause incomplete blinking, lagophthalmos, and reduced lacrimal pump function causing tearing. Depending on the severity of eyelid eversion, surgical repair involving lengthening of the anterior lamella using skin grafts may be necessary. 3 Previous case series have also described the use of hyaluronic acid gel injections as a non-surgical treatment option for congenital ectropion. 9 

> Congenital entropion

Entropion is defined as an inward rotation of the eyelid margin. Congenital entropion occurs due to a deficiency in the posterior lamella (defined as the tarsus and palpebral conjunctiva), defects in the tarsal plate such as a fold, or dysgenesis of the lower eyelid retractors. 1, 3 Inward rotation of the eyelid margin changes the position of the eyelashes, which can result in contact of the eyelash with the cornea, causing irritation and possibly scarring of the cornea, making surgical repair of the entropion necessary. 

> Congenital ptosis

Congenital blepharoptosis is a drooping of the upper eyelid secondary to embryological dysgenesis of the levator muscle that is replaced by fat or fibrous tissue. 10 It is important to note that congenital ptosis can result in amblyopia of the affected eye either due to sensory deprivation if the upper eyelid occludes the visual axis at the level of the pupil or due to astigmatism induced by the weight of the eyelid on the cornea. 

Evaluation of ptosis should primarily include an evaluation of marginal reflex distance 1 (MRD1) and levator function. MRD1 refers to the distance (in millimeters) from the upper eyelid margin to the corneal light reflection centered on the pupil with the patient facing forward in the primary position. 11 MRD1 reflects the degree or severity of ptosis. A negative MRD1 or 0 indicates that the eyelid is covering the visual axis, putting the neonate at risk of developing deprivation amblyopia. Levator function refers to the change in the vertical height of the palpebral fissure as the patient transitions from looking down to looking up. It reflects the integrity of the levator muscle and may influence the selection of surgical techniques. 1, 3, 12

There are several surgical techniques to treat congenital ptosis. In a patient with moderate ptosis, a levator muscle resection may be performed. In patients with severe ptosis, however, a frontal suspension or sling is performed to allow the patient to elevate the eyelid by recruiting the frontalis muscle. 3, 12, 13 The timing of congenital ptosis repair depends on both its severity and evidence of amblyopia. In patients in whom deprivation amblyopia is concerning and the eyelid covers the visual axis, surgery may be necessary in the first weeks of life; Therefore, it is important to recognize congenital ptosis and ensure timely referral to ophthalmology for evaluation. 

Although the most common cause of congenital ptosis is levator muscle weakness, there are also neurogenic etiologies of ptosis that can occur in neonates or young children. These include congenital oculomotor nerve palsy, Horner syndrome, and Marcus-Gunn jaw blink syndrome. Oculomotor nerve palsy may include concurrent deficits in extraocular motility including supraduction, infringement, and adduction, as well as mydriasis, depending on the degree of cranial nerve involvement. 3

Congenital Horner syndrome manifests as ptosis, miosis of the affected pupil, anhidrosis, and heterochromia of the iris. Reverse ptosis, in which the lower eyelid is raised, is also seen in congenital Horner syndrome. Birth trauma is a common cause, but it is important to recognize that neuroblastoma, an adrenal neoplasm, can also lead to congenital Horner syndrome and should be considered and investigated with imaging tests, especially if there is no clear history of birth trauma. . 14 Finally, Marcus-Gunn syndrome of mandibular blinking is due to a synkinesis that joins cranial nerves V3 and III, so that the ptosis eyelid can be elevated with mandibular movement towards the contralateral side. fifteen 

>> Variations of the palpebral epicanthus 

Epicanthus refers to the skin folds that cross the medial canthus due to the immaturity of the bone structure of the midface. There are 4 types of epicanthic folds: tarsalis (upper eyelid fold), inversus (lower eyelid fold), palpebralis (symmetrical folds of the upper and lower eyelids) and supraciliaris (upper eyelid fold that extends from near the eyebrow) . 1 Recognizing the epicanthal folds themselves when they are present may be more useful to the pediatrician or neonatologist than identifying the specific variety. 

Epicanthal folds can be seen in normal infants. In particular, the tarsal epicanthus is frequently seen in the Asian eyelid. However, epicanthic folds may also be indicative of other syndromes. For example, epicanthus inverse is a feature of BPES. This syndrome presents 4 characteristic anomalies of the eyelids: blepharophimosis, ptosis, epicanthus inversus and telecanthus.

Blepharophimosis refers to a horizontal and vertical shortening of the palpebral fissures, and telecanthus refers to an increase in the distance between the medial canthus. Previous studies have shown that 41% of patients with BPES have amblyopia and 20% have concurrent strabismus. 16 Therefore, recognition of this syndrome due to its characteristic features warrants early referral to ophthalmology for evaluation and monitoring of these visually significant complications. BPES can be secondary to a sporadic or autosomal dominant mutation in the FOXL2 gene and has been associated with primary ovarian failure in affected women. 17 

Prominent epicanthal folds can also create the illusion of esotropia, leading to pseudoesotropia.1 This is due to reduced nasal exposure of the sclera, so that the eyes appear crossed to the uninformed examiner. Using a flashlight, the corneal light reflex in each eye should be examined (Hirschberg test). If light reflections appear centered in the pupil and symmetrical, it is likely pseudoesotropia and will improve spontaneously over time. However, a corneal light reflex that appears temporally displaced over the pupillary margin or iris suggests true esotropia and warrants ophthalmologic evaluation.

>> Epiblefaron

Epiblepharon occurs when the skin of the eyelid and the pretarsal orbicularis muscle override the margin of the eyelid, giving rise to a vertical and/or inward trajectory of the eyelashes. (1)(3) It most frequently affects the lower eyelids and is more common in Asian newborns. Epiblepharon differs from congenital entropion, since in the former, the eyelid margin maintains a normal anatomical position, while in the latter, the eyelid margin itself is turned inward. This distinction is important, since epiblepharon usually resolves spontaneously as the child grows. Mild cases may be observed or treated with topical lubricating eye drops to prevent eyelash irritation. However, if there is significant contact between the eyelashes and the cornea causing recurrent corneal abrasions or scarring, surgical repair is indicated. 1, 3 

The identification of orbital anomalies that occur in the neonatal period is essential to determine those that pose a visual threat.

Furthermore, orbital anomalies often occur simultaneously with other craniofacial and systemic anomalies. Discussion of all orbital neoplasms, cysts, inflammatory conditions, or structural abnormalities that occur in the neonate or young infant is beyond the scope of this review; The authors focus on the most commonly found ones. 

>> Congenital orbital anomalies 

> Orbital manifestations of craniosynostosis

Craniosynostoses are a group of disorders whose common hallmark is the premature closure of one or more cranial sutures . Depending on the suture affected and the degree of involvement, specific cranial deformities may occur. Craniosynostosis syndromes such as Crouzon, Apert, and Pfeiffer syndromes may also present with other systemic and neurological abnormalities.

The most common orbital abnormality in craniosynostoses is orbital hypertelorism , which is a widening between the orbits. In orbital hypertelorism, the internal canthal distance, external canthal distance, and interpupillary distance are increased. Other findings include shallow orbits, proptosis, and orbital rotation. Proptosis can cause lagophthalmos and exposure of the cornea. Orbital rotation contributes to characteristic strabismus patterns, observed in 90% of patients. 3 These findings contribute to the risk of amblyopia; therefore, patients require shared treatment with an ophthalmologist. 

>> Orbital manifestations of cleft syndromes

> Goldenhar syndrome. Goldenhar syndrome (oculoauriculovertebral dysplasia) is caused by abnormal development of the first and second branchial arches. (3) This results in hemifacial microsomia with preauricular skin tags, conjunctival dermolipomas, limbal dermoids, and eyelid colobomas, as mentioned above. 3 Duane syndrome with associated strabismus is found in 25% of affected patients. 3

> Treacher Collins syndrome. Treacher Collins syndrome (also known as mandibulofacial dysostosis) is an autosomal dominant cleft syndrome whose main features include ear malformations, conductive hearing loss, and hypoplastic zygoma. 3 It is caused by an abnormal development of the first and second branchial arches. Affected patients present with depressed lateral orbital rims and lateral canthus.3 Other reported ocular findings include strabismus, nasolacrimal obstruction, refractive error, and amblyopia.3 

> Amniotic band syndrome. Variable amniotic banding clefts may occur due to mechanical effects on the developing fetus.3 When these bands occur near the orbit, bony orbital clefts may appear. Other ophthalmic manifestations include eyelid colobomas, ptosis, ectropion, corneal opacities, and tear problems.3 

>> Orbital tumors 

Orbital tumors in the neonate are rare, and most are congenital hamartomas or choristomas. Although clinical examinations can often confirm the diagnosis, imaging is sometimes necessary to differentiate between potential diagnoses.3 If imaging is sought, sequences dedicated to the orbit with appropriately thin slices are especially important. Computed tomography provides superior resolution of bony architecture, while magnetic resonance imaging (MRI) offers greater resolution of soft tissue details without radiation exposure; however, MRI will likely require sedation or anesthesia due to its duration. 3 

> Infantile hemangioma . Periocular infantile hemangiomas are hamartomas of proliferating capillary endothelial cells that follow a natural history of rapid proliferation and growth during the first year of age, followed by a varied rate of regression and involution. 1, 3 During the proliferative phase, these lesions not only become more clinically evident, but can be amblyogenic, either due to induced corneal astigmatism or due to deprivation if they obstruct the visual axis. 

Diagnosis is usually made by examination; however, MRI or ultrasound can be used to determine the posterior extent of the lesion if it is unclear, as hemangiomas can be preseptal, intraorbital, or mixed. 18 Associated systemic syndromes include PHACE syndrome, Kasabach-Merritt syndrome, and diffuse neonatal hemangiomatosis. 18 PHACE syndrome refers to a constellation of posterior fossa malformations, hemangiomas, arterial lesions, and cardiac and ocular anomalies. Ocular abnormalities include microphthalmia, optic nerve hypoplasia, retinal vascularization, choroidal hemangiomas, colobomas, strabismus, cataracts, and glaucoma. 18 PHACE syndrome is suspected if an infantile facial hemangioma affects 1 or more dermatomes. 18 Kassabach-Merritt syndrome refers to thrombocytopenic coagulopathy due to sequestration of platelets within the hemangioma. 18 Diffuse neonatal hemangiomatosis refers to multiple cutaneous and visceral hemangiomas involving the liver, gastrointestinal tract, and brain, and warrants suspicion in an infant who presents with 3 or more cutaneous hemangiomas. 18 

Infants with periocular hemangiomas require a complete ophthalmologic evaluation by a pediatric ophthalmologist, including refraction.

Currently, propranolol is the first-line treatment for involution of infantile hemangiomas, although its systemic use through oral administration carries risks of bradycardia, hypotension, hypoglycemia, and bronchospasm. 19, 20 In children with suspected PHACE syndrome, propranolol is avoided due to the increased risk of cerebrovascular events. 19, 20 Topical timolol can also be used to treat more superficial lesions. 21 An alternative treatment includes injection of corticosteroids into the lesion, but this carries a risk of retinal vascular occlusion and changes in skin pigmentation. 

> Dermoid and epidermoid cysts. Dermoid cysts are benign choriostomas that develop from epidermal tissue sequestered during closure of fetal suture lines. (18) This gives rise to a cyst lined with keratinized epithelium. If there are dermal appendages such as hair follicles, sweat glands, and sebaceous glands inside the cyst, it is called a "dermoid" cyst. (18) The lesion is called an "epidermoid" cyst if these dermal appendages are absent. Clinically, these lesions manifest as smooth, painless, mobile masses in the superotemporal or superonasal quadrants of the orbit. 18 Depending on the size and location of the cyst, proptosis, ptosis or strabismus may occur. Treatment consists of surgical removal paying special attention to not rupturing the cyst, as this increases the likelihood of inflammation and recurrence. 18

The tear system is responsible for the production of the tear film, as well as the movement and drainage of fluids through the eye.

The lacrimal and accessory glands produce the tear film. Tears move temporally to nasal during blinking and are channeled to points on the upper and lower nasal eyelids. From there, tears pass through the canaliculi, the lacrimal sac, and finally the nasolacrimal duct, which empties under the inferior turbinate. 1, 3, 22, 23 Disorders of the lacrimal system are usually due to insufficient tear production or reduced tear drainage. Reduced tear drainage is more common, but affects vision less. 3 

>> Congenital obstruction of the nasolacrimal duct 

Nasolacrimal duct obstruction occurs most commonly due to retention of fine membranous tissue where the nasolacrimal duct empties under the inferior turbinate at the valve of Hasner. Symptoms may be unilateral or bilateral, and usually begin at birth or within a few weeks of life with persistent watering or crusting of the eyes.3, 24, 25

The fluorescein dye test is a simple and reliable way to evaluate the drainage system.26 Fluorescein is first instilled to color the tear film of the eye. On reexamination, 5 minutes after instillation, the persistence of the dye in the tear film indicates a decrease in tear drainage. Nasolacrimal duct obstruction resolves spontaneously in 90% of cases by one year of age; therefore, conservative treatment with observation and lacrimal massage is initially preferred. If symptoms persist after 12 months of age, probing and dilating the nasolacrimal duct may be considered, although the exact timing and effectiveness of this procedure remains controversial.3, 24, 25

>> Dacryocystocele 

A dacryocystocele is a congenital inflammation of the lacrimal sac and nasolacrimal duct due to obstruction of the upper and lower portions of the drainage system that traps fluid inside.23, 24, 27 It usually presents at birth as a tense, bluish swelling beneath of the medial canthus. 27, 28 These dacryocystoceles are prone to infection and require urgent treatment by an ophthalmologist using decompression. If the dacryocystocele is already infected, the neonate usually requires inpatient administration of systemic antibiotics, close observation, and decompression of the dacryocele.29 The dacryocele can be decompressed with massage, but if unresponsive, a catheterization procedure is necessary to treat the obstruction. Nasal cysts have been associated with these dacryocystoceles, and may be associated with respiratory difficulties due to nasal obstruction; therefore, urgent treatment with endoscopic debridement is warranted. 29

>> Alacrimy 

Alacrimia, which refers to the underproduction of tears, is rare and arises from an ectopic or absent lacrimal gland.3 It can be associated with systemic conditions such as Riley-Day syndrome (familial dysautonomia), anhidrotic ectodermal dysplasia, or Allgrove (alacrima, cardiac achalasia and adrenal insufficiency).3

>> American Board of Neonatal-Perinatal Pediatrics Content Specifications 

- Know the syndromes associated with ocular anomalies, including craniofacial anomalies, coloboma, anomalies of the orbit, eyebrows, eyelids, eyelashes, cornea, iris and retina. 

- Know the causes and treatment of excess tearing. 

- Know the benefits and complications of ocular prophylaxis (for example, nasolacrimal duct obstruction).

The periocular adnexa includes the eyelids, the orbital bones and their contents, the lacrimal gland, and the drainage system. These structures protect the eyeball and the optic nerve. Alterations affecting these structures, their absence or malfunction can be considerably important due to the resulting exposure of the ocular surface, strabismus or amblyopia. They are also often part of syndromic conditions that warrant early intervention.

This review describes the pathologies that affect the eyelids, orbits and lacrimal ducts that occur in the neonate and must be recognized early by neonatologists and pediatricians to reach the diagnosis and eventually implement timely treatment, avoiding its progression or consequences.