Eyelid Coloboma

Coloboma is a Greek word that refers to a "multiliation" or "defect." The word coloboma in ophthalmology refers to an embryological defect in different ocular tissues and can apply to the eyelid, the iris, the retina, or optic nerve. An eyelid coloboma is a congenital, full-thickness, eyelid defect, resulting from an interruption in the normal embryologic development of the eyelid. The eylid coloboma most commonly affects the upper lids, specifically at the junction of the medial and middle third of the upper lid. No lid appendages or accessory structures are usually seen within the coloboma. ^[2]

Eyelid coloboma can be classified as:

Isolated Coloboma: Isolated colobomas encompass defects that appear independently of other systemic anomalies. However, an isolated eyelid coloboma can be either simple coloboma, where no other ocular abnormality is observed other than the eyelid defect, or accompanied by Corneopalpebral Adhesions (CPA). The isolated coloboma typically occurs sporadically, but some familial instances have been identified. The genetic inheritance of isolated eyelid coloboma remains debated, but an autosomal recessive pattern has been implicated in some cases. Certain teratogenic exposures during early pregnancy (eg, radiation and specific chemical exposure) have been linked to eyelid coloboma with CPA. 

Syndromic Coloboma : Syndromic eyelid colobomas often are indicators of a broader genetic landscape, revealing themselves in tandem with other anomalies. Fraser Syndrome, characterized by mutations in the FRAS/FREM protein family, presents a variety of manifestations, ranging from epidermal blistering to renal disorders. ^[3]  Although mutations in FRAS1 or FREM2 genes appear in half of Fraser syndrome cases, the syndrome's expression can vary significantly among individuals. ^[4]  Goldenhar syndrome, on the other hand, might manifest an eyelid coloboma and is linked with a myriad of other conditions like cleft lip, congenital heart defects, and scoliosis. Its etiology can be sporadic or inherited, with diverse associated chromosomal discrepancies. ^[5]  Environmental factors, including specific drugs and toxins, have been associated with Goldenhar syndrome's onset.

Treacher Collins syndrome, or mandibulofacial dysostosis, highlights features such as an antimongoloid slant and lateral lower eyelid colobomas. ^[6]  CHARGE syndrome presents a suite of symptoms including coloboma, heart defects, and growth retardation. ^[7]  Frontonasal Dysplasia showcases conditions like orbital hypertelorism and a bifid nose. ^[8]  In contrast, Delleman-Oorthuys syndrome is known for cerebral and orbital cysts alongside facial or eye tags. ^[9]  Nasopalpebral Lipoma Coloboma syndrome brings with it peculiarities like an upper eyelid lipoma and underdeveloped maxilla. ^[10]  Lastly, the Manitoba Oculotrichoanal (MOTA) syndrome is distinguished by features such as unilateral upper eyelid coloboma and a bifid nose. ^[4]

Table 1: Syndromes associated with eyelid coloboma (Open Table in a new window)

Environmental or mechanical events during pregnancy with or without a genetic predisposition may contribute to the development of an eyelid coloboma. Isolated eyelid coloboma is mostly sporadic, with cases having de novo mutations. Moreover, cases of isolated eyelid coloboma have been described in association with radiation exposure. ^[2]  Isolated coloboma can be graded based on the sevirity of the CPA, as follows ^[2] :

• Grade 1 - Coloboma without cryptophthalmos

• Grade 2 - Coloboma with abortive cryptophthalmos

• Grade 3 - Coloboma with complete cryptophthalmos

• Grade 4 - Classic cryptophthalmos (absence of all eyelid structures and complete coverage of eye by skin)

• Grade 5 - Severe cryptophthalmos (with severe deformity of the nose and ectropion of the upper lip)

Syndromic eyelid coloboma can occur in Fraser syndrome (cryptophthalmos syndrome) and Manitoba Oculotrichoanal (MOTA) syndrome. ^{[2, 3]}  One case series of upper eyelid coloboma with or without cryptophthalmos included 26 children (age range, 1 d after birth to 15 y). ^[11]  Of these 26 children, 19 had upper eyelid coloboma, 4 had classic cryptophthalmos, and 3 had both eyelid coloboma and cryptophthalmos. Of the 19 upper eyelid coloboma cases, 5 were isolated, 11 occured in association with facial deformities, and 3 happened with a first arch syndrome (according to the Mustarde classification). In all patients with classic cryptophthalmos cases occured sporadically and were nonsyndromic.

Frequency

No epidemiological studies exist that estimate the incidence and prevalence of eyelid coloboma.

Manitoba Oculotrichoanal (MOTA) syndrome occurs in Aboriginal individuals living in the Island Lake region of Northern Manitoba.  Typical findings in affected individuals include unilateral upper eyelid coloboma or cryptophthalmos with an aberrant anterior hairline pattern on the same side of the body and anal anomalies. ^{[2, 5, 6]}

Mortality/Morbidity

Mortality usually is related to the underlaying syndrome, rather than the coloboma per se. For instance, FS has potentially life-threatening respiratory defects leading to high incidence of stillbirths. ^[2]  

Race

No known racial predilection exists for eyelid coloboma.

Sex

No known sexual predilection exists for eyelid coloboma.

Age

By definition, congenital eyelid colobomas are present at birth.

Prognosis depends on 2 factors:

- The underlaying association, either CPA and its sevirity for isolated coloboma or the assocated syndrome for syndromic coloboma.

- The size of the defect; the larger the size, the higher the risk for ocular surface disease from insuffecient lubrication and protection.  

Genetic consultation is highly recommended, especially for patients with associated syndromes. Moreover, it is important to educate patients on avoiding ocular surface damage when elected no to proceed with coloboma correction.