Continuing Education Activity

Eyelid coloboma is a rare condition that affects congenitally. It’s a very annoying and disturbing condition for the parents also. While treating the patient, parents also should be educated and brought into confidence. Eyelid coloboma in addition to being a cosmetic disfigurement affects the cornea, vision and if associated with other systemic abnormalities can cause severe morbidity. This activity reviews the evaluation and treatment of eyelid coloboma and highlights the role of healthcare professionals in evaluating and treating patients with this condition.

Objectives:

• Identify the etiology of eyelid coloboma medical conditions and emergencies.
• Review the appropriate evaluation of eyelid coloboma.
• Outline the management options available for eyelid coloboma.
• Describe some interprofessional team strategies for improving care coordination and communication to advance treatment options and improve outcomes.

Introduction

The term coloboma derives from a Greek word “koloboma,” which means mutilated or curtailed or a hole or a defect in tissue. An eyelid coloboma is a congenital full-thickness defect of the eyelid margin seen in about 1 in 10000 births and may also involve different structures of the eye: eyelids, iris, lens, ciliary body, choroid, retina, or optic nerve.[1] 

Congenital eyelid coloboma is can be unilateral or bilateral, involving one or all four lids. The defect may vary from a small marginal notch to a full-thickness absence of the entire eyelid margin involving one third to half of the eyelid. Usually, the upper eyelid is commonly affected, and the most common site is the junction between the medial and middle third of the upper eyelid. Eyelid colobomas represent an incomplete form of cryptophthalmos. Cryptophthalmos is a congenital condition in which there is a failure of differentiation of eyelid structures, and the skin passes uninterrupted from the forehead to the cheek.

Etiology

The exact cause is unknown but is said to be a form of facial cleft[2]. Many intrauterine factors such as amniotic band, inflammation, decreased placental circulation, mechanical influences, and abnormal vascular system have been hypothesized, but all remain unproven.[3][2] An eyelid coloboma is a constant feature of Treacher Collins syndrome, which is autosomal dominant with variable penetrance and expressivity. It results from a malformation of derivatives of first and second branchial arches.

Eyelid colobomas can be an isolated finding or can be associated with various syndromes mentioned below:

1. Fraser Syndrome: Cryptophthalmos, syndactyly, ear malformations, urinary tract dysgenesis, ambiguous genitalia, laryngeal/tracheal stenosis. It is autosomal recessive [4]with mutations of FRAS1, GRIP1, and FREM2 genes[5].
2. Goldenhar Syndrome: a classical triad characterizes Goldenhar syndrome: a) mandibular hypoplasia with facial asymmetry, b) ocular and auricular malformations- periauricular tags, epibulbar dermoid, microphthalmia, eyelid coloboma, and c) vertebral anomalies: scoliosis and hemivertebra.[6]
3. Treacher Collins syndrome (mandibulofacial dysostosis): Antimongoloid slant, colobomas of lateral lower eyelids, cataracts, microphthalmos, and atresia of lacrimal passages.[7] Typically intellect is normal; 50% develop conductive deafness due to malformation of ossicles—mutation of TCOF1 (over 80% of cases), POLR1C, and POLR1D genes seen.
4. CHARGE syndrome: Coloboma, heart defects, choanal atresia, growth retardation, genital abnormalities, and ear abnormalities[8]
5. Frontonasal dysplasia: Orbital Hypertelorism, bifid nose, and medical facial cleft[9] 
6. Delleman Oorthuys (Oculocerebrocutaneous) syndrome: Agenesis of the corpus callosum, cerebral/cerebellar cysts, orbital cysts, and periorbital/facial tags, punched out defects of the lip with philtrum[10]
7. Nasopalpebral Lipoma coloboma syndrome: upper eyelid and nasopalpebral lipoma, both eyelid coloboma, telecanthus, and maxillary hypoplasia. It is autosomal dominant with full penetrance[11]
8. Manitoba Oculotrichoanal (MOTA) syndrome: unilateral upper eyelid coloboma or cryptophthalmos, anophthalmia/microphthalmia, triangular growths of hair extending from scalp to eyebrow, bifid nose, omphalocele, and anal atresia/stenosis. It has autosomal recessive inheritance and mutation of the FREM1 gene.[5]

Epidemiology

Eyelid coloboma has no predilection for sex or age. It has no race predilection expect for Manitoba oculotrichoanal syndrome, which occurs in the aboriginal population of northern Manitoba.[12][5] Findings include unilateral eyelid coloboma or cryptophthalmos with aberrant anterior hairline pattern and anal atresia/stenosis.

History and Physical

Colobomas of the eyelid are rare and are associated with systemic and ocular abnormalities. Associated ocular abnormalities include dermoid, lipo-dermoid, keratoconus, coloboma of the iris, and micro-ophthalmia. The classic congenital upper eyelid defect includes a shortage of conjunctiva, tarsal plate, orbicularis oculi muscle, and skin. In addition to causing a cosmetic blemish, the defect leaves the cornea exposed, leading to exposure keratopathy and secondary bacterial infections. Also, the visual axis can be blocked, leading to amblyopia. Strabismus is also commonly found due to the presence of high refractive errors or opacities in ocular media. 

Eyelid colobomas fall under the group of facial clefts disorders. The spectrum can extend from a complete cryptophthalmos to a small notch in the lid margin. Nouby, in a case review, has graded eyelid coloboma with cryptophthalmos into 5 Grades, grade 1 being the mildest (coloboma alone), and Grade 5 being the severe form (severe cryptophthalmos with nose and lip deformity).[13]

Evaluation

In addition to clinical eye and whole-body examination, the following investigations ( subject to fitness and contraindications for the investigations) would help detect other systemic deformities:

• X-ray chest and extremities
• CT scan brain and head
• MRI scan for abdomen
• Ultrasound abdomen

Treatment / Management

Medical management: Corneal protection and amblyopia management is the primary goal in medical treatment. Artificial tears and ointment, moist chamber optical bandages, and bedtime patching will help protect the cornea. Arrange for an interprofessional evaluation to rule out systemic deformities. Amblyopia should be anticipated in all patients with lid coloboma, as astigmatism is common. Epibulbar dermoids seen in Goldenhar syndrome induce astigmatism and can obstruct the pupillary axis and can cause amblyopia.

Surgical management: The surgical technique and timing of the surgery depend upon the size of the defect and the presence of corneal exposure and the general well-being of the infant in terms of fitness for general anesthesia. If the defect is small with no corneal exposure or obstruction of the visual axis, the surgery can be delayed until 3 or 4 years of age. Moreover, there could be contraindications for general anesthesia due to defects in the palate or poor general conditions to thrive[14][15]. Defects are graded as small (less than 25% of the length of lid margin), moderate ( 25 to 50 % defect), and severe ( more than 50%). In severe defects, both cosmetic and functional results are difficult to obtain.

Surgical management of eyelid colobomas are as follows[16]:

1) Upper eyelid reconstruction

Small defects: Direct appositional closure, direct appositional closure with lateral cantholysis, direct appositional closure with Tenzel’s semicircular flap

Moderate defects: Direct appositional closure with Tenzel’s semicircular flap Mustarde’s lid switch flap and Cutler-Beard reconstruction

Severe defects: Cutler Beard Method and Mustarde’s lid switch flap

2) Lower eyelid reconstruction

Small defects: same as upper eyelids         

Moderate defects:

• Posterior lamella: Hughes tarsoconjunctival flap
• Anterior lamella: Advancement of cheek skin, full-thickness skin graft, Tripier Flap unipedicle

Large defects:

• Posterior lamella: Chondromucous graft, palatal mucoperiosteal flap
• Anterior Lamella: Mustarde’s cheek rotation flap, nasolabial flap, medial forehead flap, lateral temporal flap  

The surgical principles of commonly used surgical techniques are as follows[17][18][19][20][21]:

1. Direct closure: Direct closure is the choice for small defects. The defect is closed in layers and is especially useful in upper eyelid congenital simple colobomas. Cantholysis of the upper crux of the lateral canthal tendon helps in relieving sutural tension. Tense lids interfere with lid movement and can cause entropion/ectropion, depending on the repair.
2. Tenzel “semicircular” flap: For central defects that cannot be closed directly, a superiorly/Inferiorly based semicircular flap can be transposed from the lateral canthal area.
3. Cutler-Beard “bridge flap” procedure: First described in 1955, is used to repair full-thickness upper eyelid defects. The principle is to bring full-thickness lower eyelid tissue, harvested from 4 mm below the lower eyelid margin, over the cornea to fill the upper eyelid defect. The full-thickness flap is divided two months following surgery at the level of the upper eyelid margin. Disadvantages are the long time lag required for lid separation, so it is not useful for monocular patients and is amblyogenic. Other disadvantages are the risk of entropion and loss of eyelashes.
4. Hughes “tarsoconjunctival” flap: Dr. Wendel Hughs in 1937 described this procedure to repair full-thickness lower eyelid defects involving more than 50 percent of the lid length. It is a two-stage procedure with the first stage involving the advancement of tarsoconjunctival flap from the upper eyelid and the second stage involving the reconstruction of the posterior lamella of the lower eyelid. The flap width should be less than the defect size. Reconstruction of the lower lid anterior lamella is done using a skin-muscle advancement flap, local skin, or free full-thickness skin graft. In the second stage of the procedure, severance of the flap is done 3 to 4 months after the initial stage. The modified Hughes procedure includes sparing of the marginal (4 mm) upper lid tarsus (provides stability to upper eyelid margin) and removal of the levator muscle aponeurosis from the tarsoconjunctival flap.
5. Mustarde’s cheek rotation flap: This flap is particularly useful for reconstruction involving larger, especially vertical defects of the lower lid. Lower eyelid defects involving the entire lower eyelid may be reconstructed using a Mustarde’s cheek rotation flap. A large skin muscle flap is rotated from the cheek to repair large lower eyelid defects. The posterior lamella can undergo reconstruction with tarsoconjunctival, nasal cartilage, or mucous membrane grafts.

Differential Diagnosis

1. Idiopathic
2. Fraser syndrome
3. Goldenhar syndrome
4. Treacher Collins syndrome (mandibulofacial dysostosis):
5. CHARGE syndrome
6. Frontonasal dysplasia
7. Delleman Oorthuys (oculocerebrocutaneous) syndrome
8. Nasopalpebral lipoma coloboma syndrome
9. Manitoba oculotrichoanal (MOTA) syndrome

Prognosis

Prognosis is good for small and moderate defects both in terms of anatomical reconstruction of the defect and functionality of the lid. In severe defects, it may be difficult to achieve a good cosmetic effect. Moreover, the associated astigmatism and eye coverage in lid sharing surgeries could cause amblyopia.

Complications

1. Exposure keratopathy
2. Infective keratitis
3. Astigmatism
4. Amblyopia
5. Strabismus
6. Cosmetic disfigurement

Deterrence and Patient Education

• Parents need to be reassured regarding cosmetic blemish and counseled to have realistic expectations.
• During counseling and education, emphasis should be given to improving the functionality of the lid and to retain the visual potential of the eye.
• Genetic consultation is essential in children with associated syndromes, especially Treacher Collins syndrome, as it is transmitted autosomal dominantly.

Enhancing Healthcare Team Outcomes

• Management requires a multidisciplinary approach because of its association with other ocular and systemic pathologies.
• Interdisciplinary liaison should be adopted to ensure the proper growth of the child while minimizing complications.
• The entire team should work together to ensure balanced mental growth along with handling the cosmetic blemish for the child.