Jonathan H. Salvin



• Congenital coloboma (plural: “colobomata”) is a defect manifesting as a cleft or gap due to the incomplete closure of the fetal (choroidal) fissure:

– Unilateral or bilateral, typically located in the inferonasal quadrant

– Isolated or associated with other intraocular anomalies or multisystem anomalies


• 2.6 per 10,000 births in the USA (1)[C]


• Microphthalmia:

– Numerous genetic defects, chromosomal aberrations, systemic syndromes

– Possibly teratogens, such as thalidomide and alcohol

– Prenatal vitamin A deficiency has also been implicated


• Key coloboma-associated disease genes include Sonic hedgehog (SHH), PAX6, MAF1, CHX10, OTX2, CHD7 (CHARGE syndrome), GDF6, CRYAA, and DPD:

– 15% cases are isolated, 58% occur in conjunction with other congenital anomalies, and 27% as part of a well-defined multisystem syndrome (5)[C].

– Isolated forms are most often sporadic, but can be autosomal dominant, autosomal recessive, or X-linked recessive (least common).

– Most common multisystem syndrome is CHARGE (MIM 214800) (6)[C].

– Syndromic forms can be autosomal dominant (i.e., Papillorenal syndrome, PAX2, isolated optic nerve “coloboma”), autosomal recessive (i.e., Meckel–Gruber syndrome, MKS1), X-linked recessive (i.e., Lenz microphthalmia syndrome, BCOR), or X-linked dominant (i.e., Goltz focal dermal hypoplasia).


• Genetic counseling and/or prenatal testing (if gene mutation or syndrome known in family):

– Avoidance of in utero exposures to teratogens


• Failure of the fetal fissure to close during the 5th to 7th week of gestation:

– Primary defect is a failure of closure of the retinal pigmented epithelium resulting in the failure of neural crest differentiation of underlying choroid, and dysplastic differentiation of overlying sensory retina (intercalary membrane), or a complete absence of overlying iris.

– Timing of the defect may explain the associations with specific systemic malformations.


• Multiple genetic mutations and chromosomal defects have been identified:

– Infection or teratogen exposure in utero

– Intrauterine vitamin A deficiency

– Idiopathic


• Microphthalmia with or without cyst:

– Visual field defect (superior scotoma)

– Nystagmus

– Lens notch may be present due to deficient zonules in the area of ciliary body coloboma (there is no true lens coloboma).

– Other systemic malformations (6)[C]



• Detailed family history of coloboma or related congenital ocular disease (family members may have asymptomatic coloboma) pregnancy and birth history, known exposure to infection or teratogen in utero:

– Other known associated systemic anomalies

– May have history of leukocoria


• Vision assessment.

• Slit-lamp exam and indirect ophthalmoscopy (with general anesthesia as needed):

– Iris coloboma will appear as a pupil notch in the inferonasal quadrant (“keyhole” pupil). It may have mild forms with absent collarette or deficient iris stroma in the same quadrant.

– Chorioretinal coloboma appears as a sharply demarcated, white, excavation in the fundus. It may have overlying retinal vessels or hyperpigmented edges.

– Strabismus and nystagmus assessment

– Assess visual fields for superior scotoma

– Perform accurate refraction, as risk of amblyopia is high

– Assess for retinal detachment

– Assess for the presence of foveal reflex when macula involved

– Thorough systemic examination for other anomalies

– Full dilated exam and careful iris slit lamp of family members



Initial lab tests 3)[C],(6)[C]

• Karyotype and microarray if systemic abnormalities not in keeping with a recognizable syndrome

• Specific genetic analysis based on the clinical diagnosis of systemic syndrome

Follow-up & special considerations

• Genetics consult


Initial approach (3)[C]

• Ultrasound to confirm coloboma and assess for the presence of orbital cyst if not clinically apparent:

– A scan for axial length and possible microphthalmia

– Brain MRI to assess for CNS pathology especially if bilateral optic nerve involvement

Follow-up & special considerations

• Radiographs, echocardiogram, and audiology evaluation as indicated in some cases:

– Examine every 6 months for retinal detachment (NOTE: Breaks will be in intercalary membrane within coloboma)

Diagnostic Procedures/Other

• Genetic counseling and molecular genetic testing as appropriate and available

Pathological Findings

• Defective, dysplastic, or absent segment of ocular tissue:

– Overlying retina is dysplastic and gliotic with rosettes sometimes present. RPE at the edge of defect is hyperplastic (2)[C]


• Morning glory disk anomaly (may be considered a form of optic nerve coloboma):

– Optic nerve pits (may be considered a form of optic nerve coloboma)

– Optic nerve hypoplasia

– Optic nerve staphyloma

– In papillorenal syndrome, the abnormal optic nerve is not truly colobomatous but larger with an enlarged cup.

– The term “macular coloboma” has been used to describe a geographic defect of the macula as seen in Leber congential amaurosis or infections such as toxoplasmosis or amniocentesis needle injury. This is an incorrect use of the term coloboma (i.e., fetal fissure not involved).

– Upper and eyelid coloboma are not defects of the fetal fissure.



• None for the primary disorder but may need treatment for systemic involvement


General Measures

• Maximization of visual prognosis with amblyopia therapy as indicated

Issues for Referral

• Genetic counseling, especially if family history or genetic mutation detected:

– Pediatric specialist consultation if systemic abnormalities present

– Retina surgery for detachment

– Ocularist referral if severe microphthalmia to consider prosthetic shell

Additional Therapies


• None proven or indicated


• Retinal detachment, cataract, strabismus, nystagmus surgeries as needed


Initial Stabilization

• Inpatient care required for systemic associations only



• Periodic dilated fundoscopy by an ophthalmologist for retinal detachment):

– As needed for amblyopia monitoring and treatment

– Low vision support

– As needed for any systemic involvement, if present

Patient Monitoring

• School performance, mental and physical development:

– Visual function and acuity

– Development of systemic signs and symptoms, especially if known syndrome


• Genetic counseling:

– Low vision intervention (importance of safety glasses and goggles, teaching compensation for visual field limitations, ameliorating photophobia with tinted glasses or brimmed hat, etc.)

– Special assistance in school as needed

– Support group:

– The CHARGE Family Support Group:

– International Children’s Anophthalmia and Microphthalmia Network:


• Visual prognosis varies greatly with defect, which can range from a small iris coloboma without visual consequences to a large chorioretinal coloboma with microphthalmia and cyst and profound visual impairment.

• Prognosis is worse if fovea or dysplastic optic nerve is absent:

– Overall patient prognosis also varies with any associated systemic involvement


• Amblyopia secondary to sensory strabismus or anisometropia:

– Retinal detachment

– Cataract

– Secondary glaucoma especially if coexistent microphthalmia (uncommon)

– Chorioretinal neovascularization (occurs most often at the superotemporal edge of coloboma, very rare)


1. Porges Y, Gershoni-Baruch R, Leibu R, et al. Hereditary microphthalmia with colobomatous cyst. Am J Ophthalmol 1992;114:30–34.

2. Onwochei BC, Simon JW, Bateman JB, et al. Ocular colobomata: Major review. Surv Ophthalmol 2000;45:175–194.

3. Chang L, Blain D, Bertuzzi S, et al. Uveal coloboma: Clinical and basic science update. Curr Opin Ophthalmol 2006;17:447–470.

4. Gregory-Evans CY, Williams MJ, Halford S, et al. Ocular coloboma: A reassessment in the age of molecular neuroscience. J Med Genet 2004;41:881–891.

5. Bermejo E, Martinez-Frias ML. Congenital eye malformations: Clinical-epidemiological analysis of 1,124,654 consecutive births in Spain. J Med Genet 1998;75:497–504.

6. Blake KD, Prasad C. CHARGE syndrome: Review. Orphanet J Rare Dis 2006;1:34.

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Nov 9, 2016 | Posted by in OPHTHALMOLOGY | Comments Off on Coloboma

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