|Classification and external resources|
|ICD-10||13.0, 10.3, 12.2,14.2,14.8|
- Coloboma of eyelid: Q10.3
- Coloboma (iris): Q13.0
- Coloboma of eye lens: Q12.2
- Coloboma of optic disc: H47.319
- Coloboma of choroid and retina: Q14.8
- Coloboma of macula: Q14.8
Coloboma comes from the greek word koloboma meaning mutilated, defect or curtailed. It is due to incomplete closure of the embryonic fissure also known as the optic fissure or choroidal fissure in second month of embryonic development of the fetus. It is used to describe such ocular defects of the eyelids, lens, cornea, iris, ciliary body, zonules, choroid, retina and optic nerve. It is typically located in the inferonasal quadrant of the involved structure and is often associated with microphthalmia. It can affect one eye (unilateral) or both eyes (bilateral).
Coloboma of the eyelid arises from defective eyelid development. Although this is induced by the developing globe, there is no clear evidence that eyelid coloboma results from globe abnormalities.
Coloboma of the lens is due to defective or absent development of the zonules in any segment that causes flattening of the equator of the lens. This is due to a lack of tension on the lens capsule and subsequent contraction and notching in that region. Thus, the term lens coloboma is a misnomer because there is no loss of lens tissue and is more accurately described as coloboma of the zonules and/or ciliary body. 
Coloboma of the cornea, iris, ciliary body, choroid, retina and/or optic nerve arise from failed or incomplete closure of the embryonic fissure during development. This process occurs on day 33 of gestation and allows for pressurization of the globe. As a result, there is a spectrum of disease that results from failed embryonic fissure closure ranging from mild and asymptomatic to microphthalmia to anophthalmia.
The embryonic fissure develops from eccentric invagination of the optic vesicle leaving a gap inferonasally. This gap allows the hyaloid artery to access the inner eye and is crucial for continued ocular development.
Closure of the embryonic fissure begins at the equator and then proceeds anteriorly and posteriorly. This is analogous to neural tube closure which starts in the thoracic region and proceeds rostrally and caudally. Similarly, defects in closure at either end have different results. Cornea, iris or ciliary body coloboma results from failed closure anteriorly and defects in choroid, retina and optic nerve results from failed closure posteriorly.
Vitamin A (retinol) has previously been shown to be crucial for normal eye development.
It is metabolized into retinoic acid via two reactions, the first of which is mediated by retinol dehydrogenase. Research has shown that zebra fishes with genetic mutations resulting in defects in this enzyme are functionally deficient in retinoic acid and develop ocular coloboma. If supplemented with retinoic acid, however, these fishes do not develop coloboma with suggests vitamin A deficiency as an etiology. 
Ocular coloboma due to failed closure of the embryonic fissure occurs in 0.5 to 2.2 cases per 10,000 live births.  It may be sporadic or inherited and is associated with systemic disorders in some cases.
Association with other systemic abnormalities:
There are numerous syndromic and chromosomal abnormalities associated with uveal coloboma including trisomies, duplications, deletions and pericentric inversions.
Specific disorders include:
- CHARGE Syndrome
- Basal cell nevus (carcinoma) syndrome
- Congenital contractural arachnodactyly
- Meckel-Gruber syndrome
- Sjogren-Larsson syndrome
- Humeroradial synostosis
- Oral-facial-digital syndrome (type VIII)
- Walker-Warburg syndrome
- Lenz microphthalmia syndrome
- Aicardi syndrome
- MIDAS syndrome
- Catel-Manzke syndrome
- Trisomy 13 (Patau syndrome)
- Trisomy 18 (Edwards syndrome)
- 13q deletion syndrome
- Wolf-Hirschhorn syndrome
- Cat-eye syndrome
- Linear sebaceous nevus syndrome
- Rubinstein-Taybi syndrome
- Kabuki syndrome
Association with other eye abnormalities or features:
- Difference in eye color between the two eyes (heterochromia)
- Small eye (microphthalmia)
- Increased thickness of the cornea
- Retinal malformation (retinal dysplasia)
- increase risk for retinal detachment
- Nearsightedness (myopia) or farsightedness (hyperopia)
- Poor vision or Visual Field defect
- Involuntary eye movements (nystagmus)
- Posterior staphyloma
Eyelid coloboma are usually found in the upper lid and are often isolated with the exception of an association with Goldenhaar syndrome. In contrast, lower eyelid coloboma are often associated with Treacher-Collins Syndrome.
Physical exam may reveal obvious defects in the eyelids and are typically seen at or soon after birth. Eyelid coloboma, however, can be minimal and not discovered until later in life. (Figure 2)
Lens coloboma is seen as flattening of the equator of the lens in an area of absence of zonular fibers. This is best visualized in a dilated eye and may be incidentally diagnosed as they are almost always asymptomatic. (Figure 3)
Anteriorly located coloboma often appears as a defect in the iris tissue. They are classified as “typical” if found in the inferonasal quadrant of the affected structure and “atypical” if found elsewhere. Cornea, ciliary body and zonules may also be involved. (Figure 4)
Posteriorly located coloboma can involve the optic nerve, retina, and choroid. If the retina is involved, it is reduced to glial tissue with no underlying RPE or choroid. This appears as an area of whitening often with pigment deposition at the junction of the coloboma and normal retina. If the optic nerve is involved, it can have a range of appearance from physiologic cupping to extensive retinal involvement (as shown in the figure below). The examiner should be wary during initial examination to evaluate for retinal detachment as patients with coloboma have increased risk for this to occur.
Retinal detachment and cataract are the most common complications associated with retinochoroidal coloboma. Coloboma of the posteior pole is associated with an increased risk for retinal detachment with occurs in 23-42% of patients.
Cataracts of multiple varieties are associated with coloboma including pigment deposits, subcapsular, cortical, anterior and posterior polar, and total opacification. Lens subluxation has also been reported in cases involving the zonules and or ciliary body. This is also a consideration for a patient undergoing cataract surgery.
Complications of eyelid coloboma are mainly due to corneal exposure from large upper eyelid defects resulting in exposure keratopathy and corneal ulceration if left untreated.
- Congenital amniotic band syndrome
- Eyelid trauma
- Heterochromia irides
- Iris nevi
- Iris trauma
- Iris atrophy
- Rieger syndrome
- Morning glory disk
- Congenital optic pits
- Optic nerve staphylomata
Retinochoroidal colobomata are usually easy to distinguish from inflammatory lesions and other causes of leukocoria.
Lubrication should be supplied if there is any evidence of compromised lid closure and corneal protection. Evaluation by oculoplastics is recommended to determine if and how lid reconstruction should occur.
Refractive error should be treated with corrective lenses. If severe and unable to correct with manifest refraction, consider lens extraction with IOL placement to prevent amblyopia from developing. Care should be taken, however, as zonular abnormalities exist and may complicate surgery.
Patients with bilateral uveal coloboma or unilateral coloboma plus one other systemic abnormality should be referred to genetics specialist to evaluate for systemic disorders.
Monocular precautions should be strongly considered for any patient with unilateral coloboma and resulting decreased visual acuity on the affected side.
Interval monitoring for retinal detachment should be done with a dilated fundus exam approximately every 6-12 months or sooner if indicated for patients with posterior coloboma. A risk of retinal detachment is there which may be upto 40%. Prophylactic laser of such eyes may reduce the occurrence of retinal detachment, though randomized trial for this is not yet available.
Measures such as patching should be taken to maximize visual potential of the affected side as there is often normal retina present and refractive error is often present putting patients at risk for amblyopia.
- National Eye Institute: Facts About Anophthalmia and Microphthalmia - http://www.nei.nih.gov/health/anoph/anophthalmia.asp
- Einstein Healthcare Network: The Anophthalmia Microphthalmia Registry - http://www.einstein.edu/genetic/anophthalmia-microphthalmia-registry/
- The International Children's Anophthalmia Network - http://www.anophthalmia.org/
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