From the Department of Ophthalmology (EL, CA, EH, DT, TGM, AMB), Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida; the Department of Pediatrics (MD-B), Division of Neonatology, University of Miami Miller School of Medicine, Miami, Florida; Maternal Fetal Medicine (JCC), San Juan, Puerto Rico; and South Florida Perinatal Medicine (DM), Miami, Florida.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Audina M. Berrocal, MD, 900 NW 17th St., Suite 243, Miami, FL 33136. E-mail: email@example.com
Ultrasounds are routinely performed in pregnancy to assess fetal anatomy and development.1 Serial ultrasounds have a 40% to 70% sensitivity and 99% specificity in detecting gross congenital malformations,2 and they are safe to use in pregnancy.3 Although antenatal detection of diseases such as anencephaly may not affect prognosis, early detection of diseases such as retinoblastoma may result in earlier postnatal interventions and better long-term outcomes.4
Technological advancements have led to better two-, three-, and four-dimensional ultrasonography of the fetal face and eye.5 In this case series, we report the use of intrauterine ultrasounds in detecting ocular pathologies that prompted early ophthalmic referral for examination and treatment.
A 30-year-old gravid 5 para 4 woman had a routine sonogram at 16 weeks that appeared unremarkable; however, an ultrasound at 34 weeks revealed a 3.1 × 3.0 cm heterogeneous mass extending from the fetus’s right orbit. Two- and three-dimensional ultrasounds were performed every 2 weeks to assess fetal development and tumor growth (Figs. 1A and 1B). The mother denied any family history of ocular disease or obstetric risk factors.
Figure 1. Infantile fibrosarcoma. (A) Three-dimensional ultrasound at 34 weeks’ gestation. (B) Two-dimensional ultrasound at 34 weeks’ gestation demonstrating a large hetereogenous mass extending from the fetus’s right orbit. (C) Photograph of extreme unilateral proptosis with conjunctival chemosis. (D) Axial magnetic resonance imaging featuring a large retrobulbar soft tissue mass displacing the right globe anteriorly. The stretched eyelid skin indicated the chronicity of intrauterine expansion by the large orbital tumor.
Vaginal delivery was originally planned, but concerns regarding ocular damage during passage through the birth canal led to a caesarean section at 40 weeks of gestation. After delivery, severe proptosis, exposure keratopathy, and conjunctival chemosis were observed in the right eye (Fig. 1C). Magnetic resonance imaging and computed tomography scans demonstrated a 5 × 3.4 × 3.8 cm partially encapsulated, heterogeneous, soft, intraconal mass displacing the right globe and stretching the optic nerve (Fig. 1D). At 7 days of age, the infant underwent exenteration of the right orbit. Pathology was consistent with infantile fibrosarcoma. The apical margin of the mass was positive, and the infant received an adjuvant chemotherapy regimen of vincristine, actinomycin, and cyclophosphamide. The patient is currently 2 years old without local recurrence. The left eye has normal vision and function.
A 21-year-old gravid 1 para 0 woman underwent an obstetric ultrasound at 23 weeks’ gestation that revealed a hyperechoic lens, retrolenticular stalk of tissue in the left eye only that failed to regress on subsequent ultrasounds, and microphthalmia (Fig. 2A). The hyaloid artery may be intact in 90% of patients at 23 weeks of gestation but should completely regress by 29 weeks.6 The mother delivered a 3.1-kg infant at 40 weeks’ gestation via cesarean section due to fetal distress.
Figure 2. Persistent hyperplastic primary vitreous/persistent fetal vasculature. (A) A coronal ultrasound at 23 weeks’ gestation with an arrow pointing to the congenital cataract and a retrolenticular fibrovascular stalk of tissue in the fetus’s left eye that failed to regress on subsequent ultrasounds. (B) Postnatal B-scan demonstrating a stalk of tissue extending from the optic nerve toward the lens, with possible calcification.
At 3 weeks of age, evaluation at the Bascom Palmer Eye Institute revealed a shallow anterior chamber and congenital cataract. On an ocular B-scan, a stalk of tissue spanning from the optic nerve to the posterior lens capsule was noted (Fig. 2B). A clinical diagnosis of persistent hyperplastic primary vitreous/persistent fetal vasculature (PHPV/PFV) was made, and the infant underwent pars plana vitrectomy and lensectomy at 3 weeks of age. A Baerveldt shunt was placed at 3 months of age for angle-closure glaucoma resistant to topical therapy. The patient is currently 5 years old; the last best-corrected visual acuity was 20/40 in the right eye and 2/100 in the left eye.
A 36-year-old gravid 4 para 2 woman had a sonogram at 13 weeks’ gestation that was notable for abnormally small eyes. The mother had a previous child with Fraser syndrome whose genetic profile did not match any previous known mutations. The patient underwent a subsequent ultrasound at 17 weeks that revealed hypoplastic eyes and malformed lower extremities (Fig. 3). Fetal magnetic resonance imaging confirmed bilateral orbital hypoplasia and no clearly discernible lenses. After careful discussion, the parents decided to terminate the pregnancy at 18 weeks of gestation. Autopsy revealed hypoplastic eyes, micrognathia, and malformed lower extremities with no gross abnormalities of the internal organs. A presumptive clinical diagnosis of Fraser syndrome was made by the medical examiner.
Figure 3. Fraser syndrome. (A) Coronal ultrasound obtained at 13 weeks’ gestation demonstrating hypoplastic eyes bilaterally. (B) Ultrasound of the lower extremities at 17 weeks. Arrow points to the malformed leg.
A 30-year-old gravid 2 para 1 woman obtained a sonogram at 23 weeks’ gestation that revealed ocular asymmetry. The right eye measured 1.4 cm and the left eye measured 0.85 cm. The mother delivered a 2.9-kg infant at 38 weeks’ gestation without complications. The infant underwent a dilated fundus examination at 1 week of age and subsequently had magnetic resonance imaging to evaluate for other congenital malformations; the imaging confirmed microphthalmia and further revealed a retrobulbar cyst and coloboma of the right eye. The infant had no light perception in the right eye. The left eye was normal. The child is currently 2 years old, and the vision in the left eye has remained stable.
Fifty years ago, obstetric ultrasounds provided such crude outlines of fetal anatomy that textbooks recommended simply confirming the presence of a globe in each orbit.7 The current guidelines for imaging the fetal face do not include examination of the eyes.8 However, the latest generation of ultrasonograms have such high resolution that orbital teratomas or cysts, retinoblastomas, and retinal detachments have been discovered on antenatal examinations.9,10
Early detection of ophthalmic pathology is important in prenatal and postnatal management decisions. In case 1, the obstetrician changed the planned mode of delivery due to the ultrasonographic findings of a large orbital mass. The obstetrician was also better able to coordinate postnatal referral to a tertiary care facility with clinicians experienced in orbital pathologies.
Once the patient in case 2 was stable to be transferred, she was evaluated at a tertiary care facility where she was diagnosed as having PHPV/PFV. Early surgical intervention is necessary because PHPV can cause secondary glaucoma as early as 3 months of age; cataracts, intralenticular hemorrhages, and synechiae may ensue.11 Surgical interventions before 2.5 months of life have been associated with fewer postoperative complications and better visual acuities.12,13 Our patient underwent a pars plana vitrectomy and lensectomy at 3 weeks of life but developed elevated intraocular pressures not controlled with topical therapy; the patient then proceeded to have glaucoma drainage implant surgery at the age of 3 months.
In case 3, the ultrasound findings of multi-systemic malformations and the family history of Fraser syndrome were supportive of a genetic disease. The findings influenced the patient to terminate the pregnancy. The case highlights the utility of ultrasounds in not only aiding clinicians but also helping patients determine the course of pregnancy.
For case 4, the microphthalmia prompted further investigations. Orbital imaging studies revealed concurrent retrobulbar cyst and coloboma. Microphthalmia itself does not require surgical intervention, but it was important to rule out other correctable ocular abnormalities or systemic congenital syndromes associated with microphthalmia.8 Unfortunately, early detection did not positively affect the final visual acuities of any patient in our study.
Once orbital anomalies are detected prenatally on one ultrasound, further imaging and work-up may be recommended. Serial ultrasounds may assist in monitoring tumor progression. Fetal magnetic resonance imaging may be useful in congenital, systemic abnormalities such as Fraser syndrome. In multi-systemic congenital malformations, a multidisciplinary team of specialists including ophthalmologists and geneticists should be assembled, genetic counseling provided, and the option for therapeutic abortion should be addressed. In the event of a future pregnancy, the echo sonographer and obstetrician-gynecologist may need to pay more careful attention to the fetal orbits.
Obstetric ultrasounds are safe, versatile tools for the intrauterine detection of certain ophthalmic diseases. Although sonograms are unable to provide definitive diagnoses, their increasing sensitivity in detecting ocular abnormalities in utero can provide physicians and expectant parents more time to make informed decisions, effective treatment planning, and early ophthalmology referrals.
- 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.
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- Torloni MR, Vedmedovska N, Merialdi M, et al. Safety of ultrasonography in pregnancy: WHO systematic review of the literature and meta-analysis. Ultrasound Obstet Gynecol. 2009;33:599–608. doi:10.1002/uog.6328 [CrossRef]
- Rodriguez-Galindo C, Wilson MW, Chantada G, et al. Retinoblastoma: one world, one vision. Pediatrics. 2008;122:e763–e770. doi:10.1542/peds.2008-0518 [CrossRef]
- Avni FE, Cos T, Cassart M, et al. Evolution of fetal ultrasonography. Eur Radiol. 2007;17:419–431. doi:10.1007/s00330-006-0307-1 [CrossRef]
- Achiron R, Kreiser D, Achiron A. Axial growth of the fetal eye and evaluation of the hyaloid artery: in utero ultrasonographic study. Prenat Diagn. 2000;20:894–899. doi:10.1002/1097-0223(200011)20:11<894::AID-PD949>3.0.CO;2-J [CrossRef]
- Nyber DA, Finberg HJ. The placenta, placental membranes, and umbilical cord. In: Newburgh DA, Mahony BS, Pretorius DH, eds. Diagnostic Ultrasound of Fetal Anomalies. St. Louis: Mosby Yearbook; 1990:623–675.
- Abuhamad AZACOG Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin, clinical management guidelines for obstetrician-gynecologists number 98, October 2008 (replaces Practice Bulletin number 58, December 2004). Ultrasonography in pregnancy. Obstet Gynecol. 2008;112:951–961.
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- Yen MT, Tse DT. Congenital orbital cyst detected and monitored by prenatal ultrasonography. Ophthal Plast Reconstr Surg. 2001;17:443–446. doi:10.1097/00002341-200111000-00011 [CrossRef]
- Anteby I, Cohen E, Karshai I, BenEzra D. Unilateral persistent hyperplastic primary vitreous: course and outcome. J AAPOS. 2002;6:92–99. doi:10.1067/mpa.2002.121324 [CrossRef]
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- Watts P, Abdolell M, Levin AV. Complications in infants undergoing surgery for congenital cataract in the first 12 weeks of life: is early surgery better?J AAPOS. 2003;7:81–85. doi:10.1016/S1091-8531(02)42009-5 [CrossRef]