4 Colobomata are subdivided into those with cysts, those with microphthalmos (small axial length), those with microcornea and normal axial length, and those with coloboma only. The molecular mechanisms controlling these tissue events are largely unknown.Īn interesting sub-classification has been proposed, based on corneal diameter and axial length. 11 Failure of part of the fetal fissure to close results in the clinical entity recognised as coloboma. Fusion of the edges of this fissure starts centrally at about 5 weeks and proceeds anteriorly towards the rim of the optic cup and posteriorly along the optic stalk, with completion by 7 weeks. This invagination gives rise to the optic fissure, allowing blood vessels from the vascular mesoderm to enter the developing eye. 8– 10 At around day 30 of gestation, the ventral surface of the optic vesicle and stalk invaginates leading to the formation of a double-layered optic cup. The processes that occur during formation of the vertebrate eye are well documented and include (i) multiple inductive and morphogenetic events, (ii) proliferation and differentiation of cells into mature tissue, and (iii) establishment of neural networks connecting the retina to the higher neural centres such as the superior colliculus, the geniculate nucleus, and the occipital lobes. The aim of this review is to highlight which genes are emerging as important in coloboma formation and how environment may also influence gene expression to cause coloboma. Information on the molecular mechanisms underlying coloboma pathogenesis is beginning to emerge based upon animal studies of coloboma and Mendelian genetic disorders, chromosomal abnormalities, toxic environmental agents such as drug usage, and dietary deficiency. Eyelid coloboma has also been described, but this is thought to arise from failure of the mesodermal folds to fuse at about 7–8 weeks of gestation. 7 This leads to colobomata affecting one or more areas of the eye including the cornea, iris, ciliary body, lens, retina, choroid, and optic nerve. The underlying aetiology of the phenotype is the failure of the ectodermal optic vesicle fissure to close. 6 Typically, colobomata are clefts caused by absent tissue in the inferonasal quadrant of the eye, but subtype, severity, and visual prognosis vary, depending on location and associated eye defects. 4 Coloboma has been reported in 0.6–1.9% of blind adults in Canada 5 and 3.2–11.2% of blind children worldwide.

The incidence of coloboma depends upon the population studied, ranging from (per 10 000 births) 0.5 in Spain, 1 1.4 in France, 2 and 2.6 in the USA 3 to 7.5 in China. In general, severity of disease can be linked to the temporal expression of the gene, but this is modified by factors such as tissue specificity of gene expression and genetic redundancy.Ĭongenital ocular colobomata (from the Greek koloboma, meaning “mutilated” or “curtailed”) are caused by defects in embryogenesis.

Through work to identify genes underlying inherited coloboma, significant inroads are being made into understanding the molecular events controlling closure of the optic fissure. Several studies have shown that, in addition to inheritance, environmental influences may be causative factors. Ocular coloboma can be seen in isolation and in an impressive number of multisystem syndromes, where the eye phenotype is often seen in association with severe neurological or craniofacial anomalies or other systemic developmental defects. Congenital colobomata of the eye are important causes of childhood visual impairment and blindness.

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