Uveal coloboma is a congenital eye anomaly caused by failure of closure of the embryonic fissure. The defect occurs in the optic disc, choroid, ciliary body, and iris along the embryonic fissure. Defects occurring on the lower side of the optic cup are called typical colobomas, while those in other locations (such as macular coloboma) are called atypical colobomas.
Typical iris coloboma results from failure of closure of the optic cup fissure. The optic cup surrounds the tissue that will become the contents of the eye by folding in from above, finally closing on the lower side. Therefore, typical iris coloboma is located inferiorly (slightly inferotemporally) and may be accompanied by ciliary body coloboma, choroidal coloboma, and optic nerve coloboma. Iris coloboma can occur alone, but it is often combined with other uveal colobomas.
Currently, there is no treatment that can “cure” iris coloboma itself. The goals of treatment are symptomatic management of photophobia, management and prevention of complications, and optimization of visual function.
| Indicator | Details |
|---|---|
| Prevalence (per births) | 0.5 to 0.7 per 10,000 births (genetic epidemiological study 1)) |
| Incidence (population-based, Minnesota, USA) | 2.6 per 10,000 births 9) |
| Bilateral rate | Approximately 50% 1) |
| Inheritance pattern | Sporadic, autosomal dominant (AD), autosomal recessive (AR), etc., diverse |
| Associated syndromes | May be found as a symptom of multi-organ malformations such as CHARGE syndrome (CHD7 mutation) |
The inheritance pattern is diverse; it may occur sporadically or as an autosomal dominant (AD) or recessive (AR) trait with multiple affected family members. It can also appear as a symptom of a multiple malformation syndrome such as CHARGE syndrome (CHD7 mutation, AD). Genetic counseling is recommended if there is a family history or if a syndromic condition is suspected.
The defect is located inferotemporally, widest at the pupillary margin and narrowing toward the root (keyhole pupil). It is often accompanied by microphthalmia, cataract, and choroidal coloboma.
Iris Coloboma
Location: Commonly occurs inferiorly (inferotemporally).
Appearance: Keyhole-shaped pupil deformity. Widest at the pupillary margin and narrowing toward the root.
Main symptoms: Photophobia due to impaired light regulation. Visual acuity is often good in isolated defects.
Ciliary Body Coloboma
Location: Often continuous with iris coloboma.
Features: Rarely occurs alone. Often continuous with large choroidal coloboma. Epithelium and muscle are absent.
Complications: Weakening of the zonules of Zinn. Reduced lens support.
Choroidal Coloboma
Findings: Observed as a well-demarcated, depressed yellowish-white lesion in the inferior fundus.
Complications: Retinal tear formation at the edge of the defect → high risk of retinal detachment. Involvement of the macula leads to poor visual prognosis.
Optic Nerve Coloboma
Findings: Enlargement and cupping of the optic disc. The defect extends around the disc.
Complications: Visual field defects and optic atrophy. Significant impact on vision.
According to the phenotypic classification by Hornby et al., the extent of coloboma involvement in the posterior segment is a major factor determining visual prognosis; the more the defect extends to the macula, the worse the visual prognosis8).
If iris coloboma occurs alone, vision is often good. However, if choroidal coloboma extends to the macula, vision decreases significantly and the prognosis is poor. Bilateral cases may be accompanied by nystagmus and amblyopia. Regular ophthalmologic follow-up to monitor vision and fundus findings is important.
Around the 6th to 7th week of gestation, closure of the embryonic fissure (optic fissure/choroidal fissure) occurs. Closure begins at the inferior equator and progresses bidirectionally toward the posterior pole and the periphery. Therefore, defects tend to remain in the posterior pole choroid and the inferior iris. If closure is incomplete, defects form in the inferior uvea (iris, ciliary body, choroid) and the optic nerve.
Regarding environmental factors, animal experiments have reported the involvement of teratogenic substances, but established risk factors in humans are limited2).
Various gene mutations have been shown to be involved in coloboma2).
| Gene | Inheritance Pattern | Associated Phenotype |
|---|---|---|
| PAX2 | AD | Papillorenal syndrome |
| CHD7 | AD | CHARGE syndrome (described below) |
| SOX2 | AD | Anophthalmia/microphthalmia + coloboma |
| VSX2 | AR | Microphthalmia + coloboma |
| SHH | AD | Holoprosencephaly + coloboma |
| GDF6 | AD | Microphthalmia/coloboma |
| GDF3 | AD | Microphthalmia/coloboma |
CHARGE syndrome is a multiple organ malformation syndrome caused by mutations in the CHD7 gene. Its name is derived from the acronym of its main features: Coloboma, Heart defects, Atresia choanae, Retardation of growth/development, Genital anomalies, and Ear anomalies. It is inherited in an autosomal dominant pattern, and coloboma is often the initial clue for diagnosis. Multidisciplinary collaboration is required for systemic management.
Differentiation from aniridia is clinically important. The diagnostic criteria for aniridia (Jpn J Ophthalmol 2020) explicitly list iris coloboma as a differential diagnosis4).
| Disease | Key differentiating features |
|---|---|
| Aniridia | PAX6 mutation. Iris is almost completely absent (>2/3). Often associated with keratopathy and macular hypoplasia4). Risk of Wilms tumor (WAGR syndrome) is specific to aniridia and is not usually present in iris coloboma. |
| Traumatic iris dialysis | History of trauma. Irregular iris tear with the site of injury corresponding to the trauma. |
| ICE syndrome | Acquired, unilateral. Primarily corneal endothelial abnormalities (atypical cells on specular microscopy). |
| Persistent pupillary membrane | Membranous structure remains in the pupillary area. Iris stroma is not deficient. |
It is often discovered as a keyhole-shaped pupil during anterior segment examination at birth or in infancy. Diagnosis is confirmed by slit-lamp microscopy, and dilated fundus examination checks for involvement of the choroid and optic nerve. If CHARGE syndrome is suspected, systemic evaluation of the heart, ears, and nose is performed. It may also be found incidentally during school or well-child checkups.
There is no curative treatment for iris coloboma itself. Symptomatic treatment for photophobia, the main symptom, is the starting point of therapy.
Cataract Surgery
Special characteristics: Surgery is difficult due to Zinn zonule weakness, poor pupil dilation, and microphthalmia.
Procedure: Phacoemulsification + IOL implantation. Consider using a capsular tension ring (CTR). Pupil expansion devices (e.g., Malyugin ring) may be necessary.
Options: Consider simultaneous implantation of an artificial iris (e.g., Customflex Artificial Iris) 5). This can improve cosmetic appearance and reduce photophobia.
Glaucoma Treatment
Medical therapy: Use intraocular pressure-lowering eye drops such as prostaglandin analogs, beta-blockers, and carbonic anhydrase inhibitors.
Surgery: Consider trabeculotomy or trabeculectomy (filtering surgery) in cases resistant to medical therapy.
Follow-up: Since glaucoma causes irreversible visual field damage, regular intraocular pressure monitoring and visual field testing are essential.
Retinal Detachment Treatment
Pathology: May be due to retinal tears within or at the edge of a choroidal coloboma, or tears unrelated to the coloboma.
Treatment: Vitrectomy is the standard. Prophylactic laser photocoagulation at the edge of the choroidal coloboma has been reported to be useful 6).
Prognosis: Cases with retinal detachment often have poor outcomes. Early detection and treatment are important.
Regular Follow-up
Target complications: Regular follow-up is essential for the three major complications: glaucoma, cataract, and retinal detachment.
Pediatric management: Regular assessment for amblyopia, strabismus, and ocular motility abnormalities is also important.
Follow-up frequency: Continue ophthalmology visits every 3 to 12 months depending on the condition and age.
There is no surgery to cure iris coloboma itself. The goal of treatment is symptomatic relief for photophobia and management of complications. If cataracts are present, phacoemulsification and intraocular lens implantation are performed, but the risk is high due to zonular weakness. Artificial iris (Customflex Artificial Iris) is an effective option for cosmetic improvement and reduction of photophobia. If glaucoma or retinal detachment occurs, respective surgical treatments are performed.
During embryonic eye development, the optic fissure forms after the optic cup. Around the 6th to 7th week of gestation, closure of the optic fissure begins at the inferior equator and proceeds bidirectionally toward the posterior pole and periphery. If closure is incomplete, defects form in the inferior uvea (iris, ciliary body, choroid) and optic nerve.
Closure of the optic fissure requires coordinated regulation of basement membrane remodeling, cell proliferation, and apoptosis 7). Any disruption in this complex process can lead to coloboma.
Closure of the optic fissure involves coordinated action of various molecular signals such as SHH (Sonic Hedgehog), PAX2, BMP, and retinoic acid 7). In animal models such as zebrafish and mice, mutations in pax2, shh, and vsx2 reproduce coloboma 7). These studies are elucidating the overall molecular mechanism of optic fissure closure.
In choroidal coloboma, histologically, the pigment epithelium and choriocapillaris are absent, and dysplastic neuroretina is present. Degenerated retinal tissue exists at the margin of the defect, posing a risk for retinal tear formation. This histological characteristic forms the pathophysiological basis for the high risk of retinal detachment.
Visual prognosis is often good in isolated iris coloboma, but worsens as choroidal coloboma extends to the posterior pole or macula. Bilateral cases may present with nystagmus and carry a risk of amblyopia. Additionally, retinal detachment occurs in a significant number of cases, due to retinal tears within or along the margin of the choroidal coloboma, as well as tears unrelated to the coloboma. Cases with retinal detachment often have poor prognosis.
