Optic nerve coloboma is a rare congenital eye anomaly in children resulting from a cleft of the ocular globe at the optic nerve–globe junction.1 Colobomata generally occur due to incomplete closure of fetal or choroidal tissue during the 5th to 7th week of fetal life and can involve any ocular structure, including the cornea, iris, ciliary body, zonule (lens), choroid, retina, optic disc, and/or optic nerve.1 Optic nerve coloboma occurs in approximately 1.4/10,000 live births2 and may be associated with microophthalmia or anopthalmia2–4 and orbital cyst formation.5–8
Although eyes can be detected by prenatal ultrasonography at 12 weeks of age and the hyaloid artery and lens by 14 weeks of age,9 visualization of the optic nerve–ocular globe junction region is limited.10 The American Institute of Ultrasound in Medicine, the American College of Radiology, and the American College of Obstetricians and Gynecologists do not currently recommend examination of the globe, orbit, or adnexal structures as part of routine prenatal ultrasonography11 because of inherent limitations such as operator variability, fetal position, gestational age defects, and tissue definition.12 For this reason, fetal magnetic resonance imaging (MRI) is performed when sonographic findings are equivocal or in the presence of family history of genetic disease, a prior child with a congenital anomaly, or a mother with a serious prenatal infection.13
Both optic nerve coloboma and microphthalmos with colobomatous cyst are rarely detected on routine prenatal ultrasonography. Only four cases of optic nerve coloboma have been diagnosed on prenatal MRI10,14 and two cases of optic nerve coloboma with cyst diagnosed prenatally, one by fetal ultrasonography15 and one by prenatal MRI.10 We describe a case of a fetus initially suspected to have retinoblastoma on prenatal ultrasonography who was later confirmed to have microphthalmos with colobomatous cyst in the right eye and optic nerve coloboma in the left eye.
The patient was a 20-year-old G1P0 female referred to our tertiary care center for in-depth ultrasonography and genetic counseling because a limb reduction defect was identified on routine prenatal ultrasonography at a regional hospital. The pregnancy course had been unremarkable until that time.
The ultrasonography performed at our center confirmed the presence of a limb reduction defect of the left arm resulting in an absent left hand and significant shortening of the radius and ulna. The contralateral arm and both legs were normal in appearance. In addition to the limb reduction defect, a mass of uncertain etiology was identified in the right fetal orbit (Figure 1). The possibility of retinoblastoma was raised. There was no known history of retinoblastoma in either parent or in the known extended family.
Prenatal ultrasonography appearance of a mass of uncertain etiology in the right fetal orbit (arrow).
To further delineate the etiology of this ultrasonography finding, a fetal MRI was ordered. Imaging identified microphthalmos of the right eye with the globe measuring 6 × 7 mm with orbital cyst and the left globe measuring 10 × 10 mm. A definitive intraocular mass was not identified on MRI, making retinoblastoma much less likely (Figure 2A). No abnormalities of the fetal central nervous system were identified on MRI. The mother refused an amniocentesis to obtain a fetal karyotype and chromosome microarray. The pregnancy was managed expectantly and labor was induced at 39-6/7 weeks for suspected intrauterine fetal growth restriction. The patient delivered a female child weighing 2.65 kg. APGAR scores were 9 and 9 at 5 and 10 minutes, respectively. The infant was transported to the neonatal intensive care unit for observation and evaluation of the known anomalies.
Prenatal magnetic resonance imaging showing microphthalmia of the right globe measuring 6 × 7 mm with orbital cyst and the normal left globe measuring 10 × 10 mm. (A) A definitive intraocular mass was not identified. (B) Postnatal magnetic resonance imaging confirmed the prenatal findings.
The infant’s neonatal intensive care unit course was unremarkable. A follow-up postnatal MRI identified a multiloculated, non-enhancing cystic mass in the right orbit compressing the right globe anteriorly and superiorly. The right globe was also small in caliber (Figure 2B). The infant was discharged on day 4 of life with scheduled outpatient ophthalmology follow-up. A genetics consultation was recommended given the presence of multiple anomalies but was not completed.
The infant was referred to our ocular oncology service following her prenatal findings. At 5 days of age, her examination was notable for orbital fullness, a bluish lower eyelid, and microphthalmia with superior displacement of the right eye (Figure 3) and an inferior disc coloboma of the left eye. A B-scan at 6 weeks of age demonstrated a large, irregularly shaped echolucent membrane filling the right orbital space with a small, oval-shaped echolucent membrane suggestive of a microphthalmic globe with a large surrounding cyst (Figure 4). She was followed up at 4 months of age without any intervention.
External examination showing the microphthalmic right eye with suggestion of inferior orbital fullness.
B-scan demonstrating small globe (asterisk) within a cystic cavity (arrows).
The majority of prenatally diagnosed microphthalmos reported in the literature has been via ultrasonography with the characteristic feature of an ocular diameter smaller than the 5th percentile for gestational age,15 although one reported case was diagnosed by MRI after the fetus was found to have mild ventriculomegaly.16 Of the two reported cases of prenatally diagnosed colobomatous cyst on ultrasonography15 and MRI,1 each can be identified as a lesion adjacent to the microphthalmic eye containing a coloboma.17 Optic nerve coloboma has been described on fetal MRI as a focal bulging of the ocular globe profile at the insertion of the optic nerve,10 although it may be difficult to identify even on MRI and must therefore be systematically sought.18
It is prudent to keep a wide differential diagnosis in mind after detecting any ocular abnormalities on fetal ultrasonography and/or MRI. Globe abnormalities that may mimic microphthalmos include anophthalmia and cyclopia. Because fetal ultrasonography is good at detecting abnormalities in globe size and morphology,18,19 these anomalies can be differentiated based on the following characteristics: anophthalmia by an absent or small orbit, an absent globe, and an absent lens; cyclopia by a single median orbit or absence of one orbit typically in association with alobar holoprosencephaly; and high myopia by increased ocular axial length.15
Retinal abnormalities that may mimic optic nerve coloboma are detectable on fetal ultrasonography and include delayed hyaloid artery regression characterized by high acoustic contrast against the anechoic vitreous, persistent hyperplastic primary vitreous appearing as a conical echogenicity within the globe with the base at the lens and the apex toward the retina and an increased thickness of the hyaloid artery–lens junction, retinal detachment appearing as a conical structure with its base toward the lens and its apex pointing posteriorly toward the optic nerve, and retinoblastoma appearing as an irregular, echogenic mass surrounded by a sonolucent area.15 In the case of retinoblastoma, only large tumors have been detected by fetal ultrasonography20 because both fetal ultrasonography and MRI are insensitive in detecting elevated lesions less than 3 mm in size.21
Knowing the characteristic imaging features can help in recognition of rare ocular developmental anomalies.15 Because colobomata and microphthalmos can both be associated with numerous syndromes,16,22 it is important they are detected early in development because they might potentially impact prenatal and postnatal care and counseling.
- Onwochei BC, Simon JW, Bateman JB, Couture KC, Mir E. Ocular colobomata. Surv Ophthalmol. 2000;45:175–194. doi:10.1016/S0039-6257(00)00151-X [CrossRef]
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- Olsen TW, Summers CG, Knobloch WH. Predicting visual acuity in children with colobomas involving the optic nerve. J Pediatr Ophthalmol Strabismus. 1996;33:47–51.
- Dolk H, Busby A, Armstrong BG, Walls PH. Geographical variation in anopthalmia and microphthalmia in England, 1988–94. BMJ. 1998;317:905–909. doi:10.1136/bmj.317.7163.905 [CrossRef]
- Bakir M, Sarialioglu F, Bilgic S, Akhan O. Microphthalmos with bilateral colobomatous orbital cyst accompanied by polycystic kidney disease and vacuolization of myeloid progenitor cells. Acta Paediatr. 1992;81:1054–1057. doi:10.1111/j.1651-2227.1992.tb12176.x [CrossRef]
- Kok-van Alphen CC, Manschot WA, Frederiks E, van Beuseko GT. Proceedings: microphthalmus and orbital cyst. Ophthalmologica. 1973;167:389–392. doi:10.1159/000306980 [CrossRef]
- Makley TA Jr, Battles M. Microphthalmos with cyst: report of two cases in the same family. Surv Ophthalmol. 1969;13:200–206.
- Waring GO 3rd, Roth AM, Rodrigues MM. Clinicopathologic correlation of microphthalmos with cyst. Am J Ophthalmol. 1976;82:714–721. doi:10.1016/0002-9394(76)90008-8 [CrossRef]
- Bronshtein M, Zimmer E, Gershoni-Baruch R, Yoffe N, Meyer H, Blumenfeld Z. First- and second-trimester diagnosis of fetal ocular defects and associated anomalies: report of eight cases. Obstet Gynecol. 1991;77:443–449.
- Righini A, Avagliano L, Doneda C, et al. Prenatal magnetic resonance imaging of optic nerve head coloboma. Prenat Diagn. 2008;28:242–246. doi:10.1002/pd.1955 [CrossRef]
- American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 101: ultrasonography in pregnancy. Obstet Gynecol. 2009;113:451–461. doi:10.1097/AOG.0b013e31819930b0 [CrossRef]
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- Porges Y, Gershoni-Baruch R, Leibu R, et al. Hereditary microphthalmia with colobomatous cyst. Am J Ophthalmol. 1992;114:30–34. doi:10.1016/S0002-9394(14)77409-4 [CrossRef]
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- Bremond-Gignac D, Copin H, Elmaleh M, Milazzo S. Fetal ocular anomalies: the advantage of prenatal magnetic resonance imaging [article in French]. J Fr Ophthalmol. 2010;33:350–354.
- Blazer S, Zimmer EZ, Mezer E, Bronshtein M. Early and late onset of fetal microphthalmia. Am J Obstet Gynecol. 2006;194:1354–1359. doi:10.1016/j.ajog.2005.11.010 [CrossRef]
- Maat-Kievit JA, Oepkes D, Hartwig NG, Vermeij-Keers C, van Kamp IL, van de Kamp JJ. A large retinoblastoma detected in a fetus at 21 weeks of gestation. Prenat Diagn. 1993;13:377–384. doi:10.1002/pd.1970130510 [CrossRef]
- Paquette LB, Miller D, Jackson HA, et al. In utero detection of retinoblastoma with fetal magnetic resonance and ultrasound: initial experience. AJP Rep. 2012;2:55–62. doi:10.1055/s-0032-1316465 [CrossRef]
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