Multimodal prenatal and postnatal imaging of microphthalmia with cyst

Abstract

Congenital ocular anomalies may be detected on prenatal imaging using fetal ultrasound and magnetic resonance imaging (MRI), although standard prenatal ultrasound for fetal physical development does not currently include ocular and orbital evaluation. We present the case of a male infant born at 39 weeks’ gestation with microphthalmia with cyst that was characterized using serial multimodal imaging, including fetal ultrasound and MRI, B-scan ultrasonography, ultrasound biomicroscopy, and postnatal MRI. Multiple prenatal and postnatal imaging modalities yielded comparable evaluations of the ocular and orbital pathology, validating the prenatal assessments.

Case Report

We present the case of a male infant with multiple anatomic anomalies born at 39 weeks’ gestational age (GA) to a 26-year-old mother by Cesarean section due to concerning fetal heart tracings. Fetal ultrasound at 33 weeks’ GA demonstrated fetal growth restriction, persistent left superior vena cava, single umbilical artery, persistent right umbilical vein, unilateral renal agenesis, coronal cleft vertebrae, shorter than normal long bones, and a nonspecific unilateral eye anomaly (Figure 1). These anomalies remained stable on a repeat ultrasound at 35 weeks’ GA. Magnetic resonance imaging (MRI) at 37 weeks demonstrated left microphthalmia with intraorbital cyst and systemic anomalies as previously identified (Figure 2; eSupplement 1A, available at jaapos.org).

FIG 1.

A, 2D axial view of the orbits on fetal ultrasound. B, 3D axial view, silhouette, and x-ray mode from fetal ultrasound. C, 3D tomographic imaging 2 mm slices starting from the forehead (−3) to posterior end of the orbits (4) from fetal ultrasound. D, 2D axial view of the orbital size on fetal ultrasound.

FIG 2.

A, Axial ultrasound biomicroscopy (UBM) image showing left eye with lens thickness measurement and A-scan overlay. B, Axial UBM image displaying left eye with anterior chamber depth and corneal thickness measurements. C, Axial UBM image of right eye. D, UBM image showing angle of right eye.

Genetic carrier testing and amniocentesis for chromosomal analysis were consistent with 16p11.2 microdeletion syndrome. Genetic testing for CHD7 gene mutation was negative. The mother’s medical history was uncomplicated, and she had a history of two prior uncomplicated births. There was no family history of congenital ocular or systemic disease.

After birth, the patient required extensive cardiorespiratory support, including extracorporeal membrane oxygenation and dopamine infusions. In the first week of life, he was stabilized and evaluated by multidisciplinary care teams in the neonatal intensive care unit.

On ophthalmic examination, the patient blinked to light on the right only. Left constant esotropia was present. The right pupil was round and reactive; the left pupil was miotic and nonreactive, with a relative afferent pupillary defect noted by reverse. The adnexa were grossly normal. Anterior segment anatomy was grossly within normal limits on the right. Left anterior segment examination was notable for poor pupil dilation and microcornea. The right corneal diameter was 10 mm, and the left was 6.25 mm. Dilated fundus examination revealed chorioretinal and optic nerve coloboma on the right; examination of the left fundus was limited due to poor pupil dilation.

B-scan ultrasound of the left eye revealed a small globe and a bilobed hypoechoic region in the posterior orbit (eSupplement 2A, available at jaapos.org). Ultrasound biomicroscopy (UBM) measurements included pachymetry of 640 μm (right eye) and 840 μm (left eye). Anterior chamber depth was 1.9 mm in the right eye and 1.04 mm in the left eye.

On the 23rd day of life, the patient underwent an MRI and a complete ophthalmic examination. MRI showed a bilobed cystic mass in the retrobulbar portion of the left orbit (Figure 3). Measurements of orbital and ocular structures across imaging modalities are provided in Table 1.

FIG 3.

Axial T2-weighted flair magnetic resonance imaging (MRI), with measurements indicated. A, Sagittal T2 MRI of left orbit with intraocular measurements. B, Axial T2 MRI with intraorbital cyst measurements. C, Axial T2 MRI with lens thickness measurements. D, Axial T2 MRI with measurement of left orbital contents.

Table 1.

Ocular and orbital measurements extracted from fetal US, fetal MRI, B-scan, UBM, and postnatal MRI

Imaging modality	Axial length, mm		Left orbital contents, mm	Left orbital cyst, mm	Lens, mm
	Right	Left			Right	Left
Fetal US	13.6	11.7	20.9	Lobe 1: 6.2 A/P × 11.4 transverse	4.3	4.2
				Lobe 2: 6.2 A/P × 16.2 transverse
Fetal MRI	17.6	9.3	19.4	Lobe 1: 9.6 mm × 11 mm	3.24	2.92
				Lobe 2: 6.5 mm × 4.3 mm
Postnatal ophthalmic US	17.8	<10	21	Lobe 1: 13 mm × 12 mm	3.7	4.38
				Lobe 2: 9 mm × 7 mm
Postnatal MRI	17.7	11.3	20.3	Lobe 1: 15.8 mm × 10.2 mm	3.32	3.56
				Lobe 2: 13 mm × 11.5 mm

MRI, magnetic resonance imaging; UBM, ultrasound biomicroscopy; US, ultrasound.

Twelve weeks following hospital discharge, vision was robust blink to light with reliable fixation and following in the right eye only. Management consisted of glasses for correction of refractive error and monocular protection.

Discussion

Microphthalmia with cyst is a developmental malformation characterized by a small globe and an orbital cyst formed through a communication channel due to failed closure of the optic fissure.¹ It is important to distinguish this condition from ocular tumors and cysts,^2,3 including retinoblastoma or medulloepithelioma. Microphthalmia with cyst is typically diagnosed during infancy through ophthalmic examination, A+B-scan ultrasonography, and neuroimaging.⁴ Prenatal imaging modalities have proven useful in detecting microphthalmia and intraorbital cysts prior to birth.^5,6 In our case, fetal ultrasound provided the first indication of an ocular anomaly, and fetal MRI subsequently demonstrated the orbital cyst.

Fetal MRI measurements were generally consistent with postnatal MRI and ultrasound for axial length and lens thickness, with more variation observed in the cystic eye. Compared to ophthalmic ultrasound, fetal and postnatal MRI underestimated lens thickness in both eyes, with greater discrepancies in the left. This is most likely due to differences in the position and orientation of the measured cross-section. UBM provides the ability to confirm alignment of the probe with the pupil, facilitating clear visualization of the anterior segment. Fetal ultrasound measurements for intraocular structures were less consistent with fetal MRI and postnatal modalities, which may be attributed to resolution and the plane of two-dimensional imaging.

There was lower consistency among imaging modalities regarding the cyst. Discrepancies may be due to its bilobed irregular structure and posterior location in the orbit, causing inconsistencies related to the limitations of two-dimensional imaging. This may also account for more variation in the left eye than the right.

Global hypoplasia was observed for nearly all structures of the anterior segment, with the exception of larger lens and thicker cornea. In the microphthalmic eye, the lens was larger than the contralateral eye, and larger than age-based normative data, despite the otherwise much smaller structures of the involved eye, which has not been previously reported.^7,8

To our knowledge, this is the first reported case of microphthalmia with cyst characterized using UBM. Its high resolution and practicality make UBM useful in cases of anterior segment tumors and iridociliary cysts, among other intraocular anomalies;⁹ it can help distinguish orbital cysts from other masses that can present similarly.

Although identification of microphthalmia with cyst during the prenatal period has previously been reported,^4–6 this case demonstrated consistency among multiple prenatal and postnatal imaging modalities in evaluation of microphthalmia with cyst. Although various congenital ophthalmic conditions can be identified on fetal imaging, fetal intervention is not currently available. The role of the pediatric ophthalmologist in fetal medicine is therefore limited. Fetal ocular evaluation has the key advantage of prompting timely referral to pediatric ophthalmology soon after birth. The role of the pediatric ophthalmologist in fetal medicine may expand with future technological advancement and may be more relevant in underserved areas where prenatal care is more accessible than pediatric ophthalmology.

Literature Search

MEDLINE, Emtree, and CENTRAL were searched without date restrictions for the following terms: prenatal, antenatal, fetal, fetus, MRI, magnetic resonance imaging, diagnostic imaging, multimodal imaging, ocular imaging, sonography, ultrasound, ultrasonography, eye diseases, ophthalmic disease, eye abnormalities, ocular abnormalities, ocular anomalies, ocular dysmorphism, cataract, glaucoma, anterior segment dysgenesis, anophthalmia, anophthalmos, coloboma, microphthalmia, and microphthalmos. Case reports and series, conference abstracts, and full-length articles describing identification of ocular or orbital anomalies using imaging were included. Articles without an English translation were excluded.