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Coloboma comes from the Greek word koloboma, meaning curtailed. It is used to describe a developmental defect of the eye occurring at embryonic stage. It can involve one or more ocular structures, including the cornea, iris, ciliary body, lens, retina, choroid and optic disc. It most commonly involves the inferonasal quadrant of the eye, and can be unilateral or bilateral, and is often associated with microphthalmia.
Congenital coloboma can occur as an isolated condition or as part of a number of different syndromes involving neurological, craniofacial and systemic developmental defects.
Visual prognosis varies according to the severity and site of the ocular malformation. Coloboma is an important cause of childhood visual impairment and blindness.
The estimated incidence of coloboma is about 1 in 10,000 births. Coloboma is estimated to account for 3-11% of blindness in children worldwide.
The eye develops in the embryo, from the optic cup and optic fissure. The optic fissure fuses at 5-7 weeks of development. Failure of this fusion leads to a gap in ocular tissue, known as a coloboma, typically located in the inferonasal quadrant of the eye. Colobomata also occur in other quadrants of the eye, but the embryological basis of these colobomata is unknown, and they are sometimes termed 'atypical'.
There may be genetic and/or environmental factors involved in causation. Genetic factors are sometimes clear, where there is a Mendelian pattern of inheritance or a chromosomal abnormality. In other cases, the inheritance pattern is less clear, but genetic factors are likely. There are recognised gene mutations involved in the heritable forms of coloboma, microphthalmia and anophthalmia.
Where the coloboma is inherited, there may be variation in severity between individuals, probably due to incomplete penetrance and variable expressivity of the gene.
Environmental factors may also cause congenital coloboma, including:
- Fetal alcohol syndrome.
- Vitamin A deficiency. Vitamine A has previously been shown to be crucial to normal ocular development.
- Teratogenic drugs - thalidomide, mycophenolate mofetil.
- Infections (toxoplasmosis, cytomegalovirus).
Microphthalmia, anophthalmia and coloboma are an inter-related group of congenital ocular abnormalities which can co-exist. Often there is no recognised genetic syndromic aetiology. Optic cysts are also part of this spectrum.
Described syndromes involving coloboma together with multisystem malformations coloboma include:
- CHARGE syndrome - Coloboma, Heart anomaly, choanal (nasal) Atresia, Restriction (of growth and/or development), Genital and Ear abnormalities.
- Epidermal naevus syndrome.
- Cat eye syndrome.
- Velo-cardiofacial syndrome.
- DiGeorge syndrome.
- Kabuki syndrome.
- Coloboma in association with renal anomalies.
- MIDAS syndrome (Microphthalmia, Dermal Aplasia, and Sclerocornea), an X-linked dominant disorder lethal in boys.
- Patau's syndrome (trisomy 13).
- Edwards' syndrome (trisomy 18).
- Wolf-Hirschhorn syndrome.
An extensive list of syndromes and genetic conditions associated with coloboma can be found in the review by Chang et al.
This may be limited to the iris, but can involve other parts of the eye. It may be partial or complete:
- Complete iris coloboma results in a 'keyhole-shaped' pupil.
- Partial iris coloboma involves the pupillary margin, giving an oval pupil.
- Occasionally, only the pigment epithelium is involved and the defect is not obvious, but can be seen on transillumination.
Zonule and ciliary body coloboma
- This causes a defect in the zonular fibres around the lens; the ciliary body may also be affected. (The lens tissue itself is not involved.)
- As a result, the lens may contract segmentally with a notch in the affected region.
- The condition is therefore sometimes inaccurately termed lens coloboma.
Retinochoroidal (choroidal) coloboma
- Coloboma of the cornea, iris, ciliary body, choroid, retina and/or optic nerve arises from failed or incomplete closure of the embryonic fissure during development. This process occurs on day 33 of gestation and allows for pressurisation of the globe.
- The defect is an area of bare sclera (or sometimes hypoplastic retina), usually in the inferonasal quadrant. It may involve the optic nerve (which means the optic disc).
- There is a spectrum of disease from mild, asymptomatic defect to microphthalmia to anophthalmia.
- Macular colobomata can occur, and are usually bilateral and symmetrical. Probably they are 'atypical' colobomata (see 'Aetiology', above). They may be asymptomatic or may cause visual loss, depending on the involvement of the optic nerve, macula and maculopapular bundle.
- Optic disc colobomata vary from an uninvolved disc to an unrecognisable optic nerve head.
- Certain other disc abnormalities may be a type of coloboma, although their origin is uncertain. These include:
There is a defect in the eyelid; the size of defects varies from a notch to the absence of the lid; defects may be full or partial thickness. Eyelid coloboma may have different causes, unrelated to abnormalities of the globe of the eye, and the defect occurs at a later stage in embryonic development. It is due to faulty fusion of the lid folds at about 7-8 weeks of gestation, and can be associated with other syndromes involving abnormal facial development, including Treacher Collins' syndrome.
This may be obvious, seen as a black defect of the iris. The gap may be partial or complete (see 'Iris coloboma' under 'Types of coloboma', above). A small iris coloboma, particularly if not attached to the pupil, can allow a second image to form at the back of the eye, leading to blurred or double vision, decreased acuity and 'ghost' imaging.
Chorioretinal and optic nerve coloboma
- May be asymptomatic or noticed on routine examination.
- May present as reduced visual acuity or visual field.
- May present in adulthood with visual loss due to retinal detachment (see 'Complications', below).
- The appearance is a white area of the fundus, with defined borders and often with clumps of pigment near the rim.
- May be noticed by parents or doctors as leukocoria (white pupil caused by an absent pupillary reflex).
Paediatric, family and genetic assessment
- In young children, a paediatric assessment is often appropriate to look for any associated syndrome or a linked anomaly outside the eye.
- To look for a heritable cause:
- Parents' eyes can be examined (for asymptomatic colobomata).
- Chromosomal analysis and genetic counselling are often relevant.
- Direct and indirect ophthalmoscopy - to assess choroidoretinal and optic nerve involvement.
- Accurate refraction.
- Visual field testing - if old enough to co-operate.
- Slit-lamp examination - for anterior eye structures (may require general anaesthetic in babies).
- Further investigations include:
- CT or MRI scan - for microphthalmia or associated central nervous system (CNS) defects.
- Evaluation of axial length (by ultrasound) and corneal diameter - these may help to estimate prognosis (see 'Prognosis', below).
- Optical coherence tomography - to image optic pits and choroidoretinal colobomata.
- Fluorescein angiography.
Choroidoretinal lesions can mimic:
- Healed choroiditis due to toxoplasma, Toxocara canis or Toxocara cati.
- Ocular histoplasmosis.
- Optic disc duplication.
- Age-related macular degeneration.
- Optic disc coloboma can mimic glaucomatous cupping.
- May not require treatment unless for cosmesis or photophobia.
- Cosmetic contact lenses are an option.
- Surgical repair is possible.
- Surgery to the lids may be required, depending on the size of the defect.
- Protection of the cornea is essential. Non-surgical treatment (lubricants and patches worn at night) may be used to defer surgery - eg, for very young babies.
Supportive treatment (if vision is poor)
- Information for parents.
- Correction of refractive errors and treatment for amblyopia and strabismus, if required.
- Visual aids and other low vision support.
- If only one eye has poor vision, safety glasses and the use of goggles for sport.
- For severe microphthalmia, a prosthesis assists the symmetrical development of the face.
- May have photophobia.
- May have double vision, blurring or ghosting, as detailed above.
- Exposure keratopathy and corneal ulceration, if the cornea is not protected.
- Reduced visual acuity or visual field (variable, see 'Prognosis', below).
- Anisometropia, amblyopia and strabismus secondary to the visual deficit.
- Retinal detachment is the most common complication of choroidoretinal and optic disc colobomata, occurring in up to 42% of patients.
- Retinal detachment can also occur with coloboma of the zonule or ciliary body.
- Cataracts of multiple types are associated with coloboma, including pigment deposits, which may be subcapsular, cortical, anterior and posterior polar, and can lead to total opacification.
- Lens subluxation has been associated with coloboma of the zonules and ciliary body.
- Subretinal neovascularisation can occur with retinochoroidal coloboma and may lead to macular detachment.
- Morning glory disc anomaly may have an associated encephalocele. This may present as pulsating exophthalmos or a mass in the upper lid or nasopharynx. Facial masses should not be biopsied without prior imagining.
- Cataracts (various types) are associated with coloboma.
- Secondary glaucoma due to faulty formation of fluid drainage systems in the eye. This may present later in life.
- Lens subluxation (uncommon).
The prognosis for vision depends on the severity and location of the coloboma (particularly in relation to the optic nerve, macula and maculopapular bundle) and on any complications such as retinal detachment or amblyopia.
- Vision can range from normal to no perception of light. The visual prognosis for an individual patient is difficult to predict:
- Coloboma size and optic nerve involvement do not necessarily predict poor acuity; patients can have large colobomata with optic nerve involvement and still have near-normal vision and stereopsis.
- The extent of ocular malformation and the degree of microphthalmia are considerations in estimating the visual prognosis. Therefore, in an infant with coloboma, corneal diameter and axial length are useful measurements to aid evaluation of visual potential.
- Since it is difficult to predict the final visual acuity in an infant with coloboma affecting the posterior eye, affected children need careful treatment for refractive errors and possible amblyopia.
Further reading & references
- Micro and Anophthalmic Children's Society (MACS)
- Coloboma; Royal National Institute of Blind People
- Coloboma, Ocular, Autosomal Dominant; Online Mendelian Inheritance in Man (OMIM)
- Lee BJ, Traboulsi EI; Update on the morning glory disc anomaly. Ophthalmic Genet. 2008 Jun;29(2):47-52.
- Onwochei BC, Simon JW, Bateman JB, et al; Ocular colobomata. Surv Ophthalmol. 2000 Nov-Dec;45(3):175-94.
- Gregory-Evans CY, Williams MJ, Halford S, et al; Ocular coloboma: a reassessment in the age of molecular neuroscience. J Med Genet. 2004 Dec;41(12):881-91.
- Gonzalez-Rodriguez J, Pelcastre EL, Tovilla-Canales JL, et al; Mutational screening of CHX10, GDF6, OTX2, RAX and SOX2 genes in 50 unrelated Br J Ophthalmol. 2010 May 21.
- Abdelrahman A, Conn R; Eye abnormalities in fetal alcohol syndrome. Ulster Med J. 2009 Sep;78(3):164-5.
- Merlob P, Stahl B, Klinger G; Tetrada of the possible mycophenolate mofetil embryopathy: a review. Reprod Toxicol. 2009 Jul;28(1):105-8. Epub 2009 Feb 25.
- Skalicky SE, White AJ, Grigg JR, et al; Microphthalmia, anophthalmia, and coloboma and associated ocular and systemic features: understanding the spectrum. JAMA Ophthalmol. 2013 Dec;131(12):1517-24. doi: 10.1001/jamaophthalmol.2013.5305.
- Blake KD, Prasad C; CHARGE syndrome. Orphanet J Rare Dis. 2006 Sep 7;1:34.
- Ming JE, Russell KL, Bason L, et al; Coloboma and other ophthalmologic anomalies in Kabuki syndrome: distinction from Am J Med Genet A. 2003 Dec 15;123A(3):249-52.
- Chang L, Blain D, Bertuzzi S, et al; Uveal coloboma: clinical and basic science update. Curr Opin Ophthalmol. 2006 Oct;17(5):447-70.
- Dutton GN; Congenital disorders of the optic nerve: excavations and hypoplasia. Eye (Lond). 2004 Nov;18(11):1038-48.
- Gopal L; A clinical and optical coherence tomography study of choroidal colobomas. Curr Opin Ophthalmol. 2008 May;19(3):248-54.
- Pian D, Ferrucci S, Anderson SF, et al; Paramacular coloboma. Optom Vis Sci. 2003 Aug;80(8):556-63.
- Islam N, Best J, Mehta JS, et al; Optic disc duplication or coloboma? Br J Ophthalmol. 2005 Jan;89(1):26-9.
- Teoh SC, Mayer EJ, Haynes RJ, et al; Vitreoretinal surgery for retinal detachment in retinochoroidal colobomata. Eur J Ophthalmol. 2008 Mar-Apr;18(2):304-8.
- Ankola PA, Abdel-Azim H; Congenital bilateral upper eyelid coloboma. J Perinatol. 2003 Mar;23(2):166-7.
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Dr Michelle Wright
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