Coloboma is an eye abnormality that occurs before birth. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in one of several parts of the eye, including the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or the optic nerves, which carry information from the eyes to the brain.

Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision. Colobomas affecting the iris, which result in a "keyhole" appearance of the pupil, generally do not lead to vision loss. Colobomas involving the retina result in vision loss in specific parts of the visual field. Large retinal colobomas or those affecting the optic nerve can cause low vision, which means vision loss that cannot be completely corrected with glasses or contact lenses.

Some people with coloboma also have a condition called microphthalmia. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss.

People with coloboma may also have other eye abnormalities, including clouding of the lens of the eye (cataract), increased pressure inside the eye (glaucoma) that can damage the optic nerve, vision problems such as nearsightedness (myopia), involuntary back-and-forth eye movements (nystagmus), or separation of the retina from the back of the eye (retinal detachment).

Some individuals have coloboma as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When coloboma occurs by itself, it is described as nonsyndromic or isolated.

Colobomas involving the eyeball should be distinguished from gaps that occur in the eyelids. While these eyelid gaps are also called colobomas, they arise from abnormalities in different structures during early development.

Coloboma comes from a Greek word which means “curtailed”. It is used to describe conditions where normal tissue in or around the eye is missing from birth.

To understand coloboma, it is useful to be familiar with the normal structure and appearance of the eye, and the terms related to the different parts of the eye.

There are different kinds of coloboma, depending on which part of the eye is missing. Coloboma can affect the:

• Eyelid
• Lens
• Macula
• Optic nerve
• Uvea

Eyelid coloboma

In eyelid coloboma, a piece of either the upper or lower eyelid is absent. Eyelid coloboma may be part of a genetic syndrome or happen as a result of a disruption of eyelid development in a baby. A syndrome is a specific grouping of birth defects or symptoms present in one person (www.genome.gov).

Lens coloboma

In this type of coloboma, a piece of the lens is absent. The lens, which helps focus light on the retina, will typically appear with a notch.

Macular coloboma

This happens when the center of the retina, called the macula, does not develop normally. The macula is responsible for daylight, fine and color vision. Macular coloboma may be caused when normal eye development is interrupted or following an inflammation of the retina during development of the baby.

Optic nerve coloboma

Optic nerve coloboma refers to one of two distinct things:

1. An abnormal optic nerve that is deeply “excavated” or hollowed out. In some cases, it can also be referred to as an optic nerve pit. The optic nerve is the bundle of nerve fibers that relays the light signals from the eye to the brain.
2. A uveal coloboma that is large enough to involve the optic nerve, either the inferior portion or the entire optic disc.

Uveal coloboma

This coloboma can present as an iris coloboma (the iris is the colored part of the eye), with the traditional “keyhole” or “cat-eye” appearance to the iris, and/or as a chorio-retinal coloboma where the retina in the lower inside corner of the eye is missing.

Uveal coloboma is a rare condition that is not always well documented. Depending on the study and where the study was conducted, a majority of estimates range from 0.4 to 5 cases per 10,000 births. Some cases may go unnoticed because uveal coloboma does not always affect vision or the outside appearance of the eye.

Uveal coloboma is a significant cause of blindness. Studies estimate that 5 to 10 percent of blind European children have uveal coloboma or uveal coloboma-related malformations.

It is believed that uveal coloboma is primarily genetic in origin. “Genetic” means that the coloboma was caused by a gene that was not working properly when the eye was forming. Sometimes coloboma is part of a specific genetic syndrome, for which the genetics are known. For instance, coloboma is one feature of CHARGE syndrome, which is associated with a change in, or a complete deletion of a gene called CHD7 in most cases.

Researchers have found genes associated with an eye malformation in the microphthalmia, anophthalmia, coloboma (MAC) spectrum in up to 20% of cases. To date, however, we still do not know which genes explain most cases of coloboma.

Some researchers have proposed that certain environmental factors may contribute to developing coloboma, either in humans or in animals. These findings have been published over time in the research literature, but there has been no systematic analysis of possible links. For instance, it is known that babies exposed to alcohol during pregnancy can develop coloboma — but they also have other anomalies. There are no known strong links between environmental exposures and isolated coloboma.

It is always possible that coloboma happens strictly by chance. In summary, there is little data to presently say why coloboma happened to a person in a family where no one else is affected.

How does uveal coloboma happen?

To understand how uveal coloboma happens, we first have to understand how the eye forms in the developing baby. The eyes start as stalks coming out of the brain. The tip of each stalk will become the eye itself, while the rest of the stalk will become the optic nerve linking the eye to the brain. There is a seam at the bottom of each stalk, where blood vessels originally run. This seam is known as the optic fissure, or the choroidal fissure, or the embryonic fissure. Starting at the fifth week of gestation (pregnancy), this seam must close. The closure starts roughly in the middle of the developing eye and runs in both directions. This process is finished by the seventh week of gestation. If, for some reason, the closure does not happen, a uveal coloboma is formed.

Depending on where the closure did not happen, the baby can have an iris coloboma (front of the fissure), a chorio-retinal coloboma (back of the fissure), or any combination of these. Uveal coloboma can affect one eye (unilateral) or both eyes (bilateral). The condition can be the same in both eyes (symmetric) or different in both eyes (asymmetric). A uveal coloboma may go from front to back (continuous) or have “skip lesions”. The fact that the seam runs at the bottom of the stalk is the reason why uveal coloboma is always located in the lower inside corner of the eye.

How can uveal coloboma be inherited?

Isolated coloboma can follow all possible patterns of single gene inheritance, namely autosomal dominant, autosomal recessive and X-linked. In one family, however, coloboma will follow only one pattern. For instance, in case of an autosomal dominant pattern, a person with coloboma would have a one in two chance of passing on the coloboma to each of his or her offspring. In families with a single case of coloboma, it is not possible to say what pattern of inheritance is involved; therefore, it is not possible to give an exact recurrence risk number. The recurrence risk of coloboma computed from averaging data across many families (empiric risk) is about 10 percent. This is an imperfect number, as it mixes information from families where this risk may be close to 0 percent with information from families where the actual risk may be 25 percent or even 50 percent.

The topic of inheritance of coloboma is complicated by several factors:

• Sometimes a person who is at risk for developing coloboma may not develop the condition, or it may be so minor that it goes unnoticed. This may appear in the family history as an inconsistent, non-interpretable pattern of inheritance.
• Knowing the pattern of inheritance of coloboma in a family does not give information on how the vision of an at-risk person will be affected. The location (front vs. back of the eye), side (left eye, right eye or both) and size of the coloboma cannot be predicted.
• There may be more than one gene involved in being at risk for coloboma, and environmental factors might play a role.

For coloboma due to a known syndrome, such as CHARGE syndrome, inheritance is based on what is known about the genetic basis of that particular syndrome. However, it is rarely, if ever, possible to say whether coloboma will be a feature of the syndrome in a person inheriting the genetic background responsible for this syndrome.

There may or may not be any symptoms related to coloboma; it all depends on the amount and location of the missing tissue. People with a coloboma affecting the macula and the optic nerve will likely have reduced vision. In general, it is difficult to exactly predict what level of vision a baby will have only by looking at how much of the retina is missing. A more precise estimate of the level of vision can be obtained over time, as the child grows and can perform more vision tests.

People with a coloboma affecting any part of the retina will have what is called a “field defect”. A field defect means that a person is missing vision in a specific location. Because coloboma is located in the lower part of the retina, vision in the upper part of the field of vision will be missing. This may or may not be noticeable to the affected person and may or may not affect performing daily activities.

A person with a coloboma affecting the front of the eye only will not have any decreased vision from it. Some people, however, have reported being more sensitive to light.

Testing may be available in cases where the coloboma is part of a specific genetic syndrome. This testing would look for the gene(s) causing that syndrome. Genetic testing is done on a blood sample and may involve looking at the patient’s chromosomes or looking at one or more specific genes on some of the chromosomes. For definition and pictures of genes and chromosomes, please visit the National Library of Medicine’s Genetics Home Reference.

To date, there is no high yield clinical test for uveal coloboma since at least 80% of cases remain unexplained. Genes that have been associated with uveal coloboma may be part of broader panel tests for conditions such as anophthalmia, microphthalmia, anterior segment dysgenesis and/or developmental eye diseases. However, results from such testing will be negative in the majority of cases.

In the eye

Coloboma is sometimes found in association with other eye features. These may include:

• Difference in eye color between the two eyes (heterochromia)
• Small eye (microphthalmia)
• Increased thickness of the cornea. The cornea is the clear front part of the eye.
• Clouding of the lens (cataract)
• Elevated pressure in the eye (glaucoma)
• Retinal malformation (retinal dysplasia)
• Nearsightedness (myopia) or farsightedness (hyperopia)
• Involuntary eye movements (nystagmus)
• Protrusion of the back of the eyeball (posterior staphyloma)

In other parts of the body

Coloboma may be an isolated feature or may be found with other features. Sometimes these other features may be few and minor, such as skin tags near the ear. Sometimes they may be more numerous and severe, such as a heart or a kidney defect. A few of these associations may be genetic syndromes. These include (but are not limited to):

• CHARGE syndrome
• Cat-Eye syndrome
• Kabuki syndrome
• 13q deletion syndrome
• Wolf-Hirshhorn syndrome

Patients with uveal coloboma should have yearly follow-up exams by an eye care professional. However, there is currently no medication or surgery that can cure or reverse coloboma and make the eye whole again. Treatment consists of helping patients adjust to vision problems and make the most of the vision they have by:

• Correcting any refractive error with glasses or contact lenses.
• Maximizing the vision of the most affected eye in asymmetric cases. This may involve patching or using drops to temporarily blur vision in the stronger eye for a limited period of time.
• Ensuring that amblyopia (lazy eye) does not develop in childhood in case of asymmetry. Sometimes amblyopia treatment (patching, glasses and/or drops) can improve vision in eyes even with severe colobomas.
• Treating any other eye condition that may be present with coloboma, such as cataracts.
• Treating any complications that might arise from a retinal coloboma later in life, such as the growth of new blood vessels at the back of the eye (neovascularization) and/or retinal detachment. These complications are rare, in the order of 1-2% based on our experience.
• Using low vision devices, as needed.
• Making use of rehabilitation services, such as early intervention programs.
• Offering genetic counseling to the patient and family members.

If the eye with the coloboma is very small (microphthalmia), other follow-ups may be needed. Conformers and expanders may be used to help support the face and encourage the eye socket to grow. Children may also be fitted for a prosthetic (artificial) eye to improve appearance. As the face develops, new conformers will need to be made.

For people who wish to alter the appearance of a coloboma affecting the front of the eye, two options are currently available:

• Colored contact lenses that make the black part of the eye (pupil) round.
• Surgery to make the pupil rounder. This procedure pulls and sutures together the lower edges of the iris.