Two cases of otherwise healthy children with no known family history of retinoblastoma who were diagnosed as having retinoblastoma after failing a visual-evoked potential test during a well-child visit are reported. This early detection allowed for eye-sparing treatment. [J Pediatr Ophthalmol Strabismus 2013;50:e41–e43.]
From Vanderbilt University Medical Center, Nashville, Tennessee (CBE, SPD); and Stamford Ophthalmology, Stamford, Connecticut (ABW).
Dr. Donahue received an unrestricted departmental grant from Research to Prevent Blindness and the Sam and Darthea Coleman Endowed Chair in Ophthalmology at Vanderbilt University. Dr. Donahue is a consultant for Welch-Allyn, Inc. (Skaneateles Falls, NY), Plus-Optix (Hillsboro Beach, FL), Pediavision (Lake Mary, FL), Pediatric Vision Screener (Boston, MA), and Diopsys, Inc. (Pine Brook, NJ). The remaining authors have no financial or proprietary interest in the materials presented herein.
Correspondence: Christopher B. Estopinal, MD, 2311 Pierce Avenue, Nashville, TN 37232-8808. E-mail:
Received: June 07, 2013
Accepted: June 21, 2013
Posted Online: August 13, 2013
Although retinoblastoma is the most common intraocular malignancy in children, there are only approximately 300 new cases that occur in the United States each year.1 Retinoblastoma is caused by inactivation of the RB1 gene, a dominant tumor suppressor gene; all bilateral and as many as 15% of unilateral cases result from germline mutations in this RB1 gene, which are inherited in an autosomal dominant fashion.2 Although retinoblastoma is often cited as a model for heritable malignancy, fewer than half of children with the disease carry a germline mutation in the RB1 gene and only 10% to 20% of affected children have a family history of disease.3 We recently encountered two cases in which a child who failed a visual-evoked potential (VEP) screening examination in a general pediatrician’s office was referred to a pediatric ophthalmologist and diagnosed as having bilateral retinoblastoma. Both were able to be treated successfully with eye-sparing therapy.
The first patient was a healthy 7-month-old female infant with no known family history of ocular disease who failed a VEP screening test using the Enfant VEP screener (Diopsys, Inc., Pine Brook, NJ) during a well-child visit with her pediatrician (Figure 1). The VEP test results recommended a referral due to a statistically significant difference in visual acuity between the right and left eyes. She was referred to a pediatric ophthalmologist, and at the time of the ophthalmology visit the parents reported an intermittent right esotropia.
Figure 1. Printout from Diopsys Enfant Vision Screening System demonstrating the magnitude (left) and phase (right) of the steady state visual-evoked potential (VEP) for the right and left eyes of the first patient. Magnitude and phase parameters were calculated from the VEP responses at each of the six spatial frequencies (from 0.4 to 12.9 cycles per degree). The patient had a normal magnitude response at the various spatial frequencies for the left eye, but no detectable response in the right eye. The high reliability coefficient (5) and the sensor color (green) indicate high validity of the test result.
Ocular examination by the pediatric ophthalmologist demonstrated no fixing or following behavior in the right eye. Vision was central, steady, and maintained in the left eye. No relative afferent pupillary defect was elicited. Sensorimotor examination revealed a variable right intermittent esotropia of up to 30 prism diopters. The external examination and anterior segment examination were normal bilaterally. Dilated fundus examination of the right eye demonstrated a cream-colored 3 × 8–mm elevated lesion in the macula that abutted the optic nerve. There were several other smaller, whitish lesions in the right eye. Examination of the left fundus demonstrated a single 3 × 4–mm cream-colored lesion in the inferior mid-periphery of the retina that was most consistent with retinoblastoma.
The patient was referred to a tertiary cancer center for further evaluation, where formal examination under anesthesia demonstrated five distinct tumors in the right eye with no vitreous seeding, the largest of which was 8 × 4 mm. The left eye had a single tumor of 3 × 4 mm located in the inferior peripheral retina.
The patient was treated with a combination of thermotherapy, cryotherapy, and intra-arterial chemotherapy. The tumors regressed over 6 months, and the child has not needed additional treatment for tumor recurrence. She remains tumor free after 2 years.
The second patient was an otherwise healthy 6-month-old female infant with no family history of retinoblastoma. At the pediatrician’s office she was able to fix and follow with both eyes. Pupils were equal, round, and appropriately reactive to light. Her red reflex was normal. Sensorimotor examination did not show any extraocular movement abnormalities. She failed a VEP screening test (Figure 2) and was referred to a pediatric ophthalmologist. At the ophthalmologist’s office a dilated funduscopic examination revealed bilateral retinal lesions.
Figure 2. Printout from Diopsys Enfant Vision Screening System demonstrating the magnitude (left) and phase (right) of the steady state visual-evoked potential (VEP) for the right and left eyes of the second patient. Magnitude and phase parameters were calculated from the VEP responses at each of the six spatial frequencies (from 0.4 to 12.9 cycles per degree). The patient had a normal magnitude response at the various spatial frequencies for the right eye, but an abnormally low response in the left eye. The high reliability coefficient (5) and the sensor color (green) indicate high validity of the test result.
The patient was referred to an ophthalmic oncologist, where examination under anesthesia revealed bilateral retinoblastoma. Three lesions were located in the right eye: a 6 × 6 × 3–mm lesion one-half disc diameter superonasal to the optic nerve, a 3 × 3 × 1.5–mm equatorial lesion, and a 5 × 5 × 2.5–mm equatorial lesion. Two lesions were found in the left eye: a 4 × 4 × 2.5–mm juxtapapillary lesion obscuring approximately 30% of the optic nerve and an 8 × 8 × 4–mm foveal-sparing superotemporal macular lesion (Figure 3). The patient was treated with a combination of thermotherapy and intra-arterial chemotherapy, and her tumors have continued to regress at 8 months after diagnosis.
Figure 3. Color fundus photographs of the second patient demonstrating bilateral retinoblastoma. The photographs are presented in standard ophthalmic fashion with (left) the right eye and (right) the left eye.
Retinoblastoma is a life-threatening condition.4 The updated United States Preventive Services Task Force guidelines recently eliminated the recommendation for preschool vision screening for 1- and 2-year-old children, noting insufficient evidence that such screening was effective.5 An accompanying invited commentary raised significant concerns about the resultant lack of screening to detect vision-threatening conditions such as cataract and life-threatening conditions such as retinoblastoma in this age group.6 The two cases reported here demonstrate the effectiveness of preschool vision screening in detecting retinoblastoma, the first by both external examination and VEP screening, and the second solely by VEP screening. Because leukocoria and strabismus are the most common presenting signs of retinoblastoma,7 it is likely that further tumor growth would have eventually brought both children to medical attention. However, many patients with bilateral retinoblastoma require enucleation of one eye for an advanced tumor,4 and we believe that early detection in both cases allowed the eye to be saved and vision preserved.
VEP testing measures a patient’s brainwave activity in response to visual stimuli. The Enfant VEP testing device uses a sweep VEP stimulus in the form of horizontal black and white bar patterns that reverse at a constant rate of 15 Hz. There are six bar sizes representing six various spatial frequencies that approximate visual acuities ranging from 20/180 to 20/40. Following the placement of three disposable electrodes in specific locations on the head, the bars are shown to the child six times. The eyes are tested monocularly at an 85% contrast level. Data are collected from both eyes and compared for statistical differences. The results are interpreted internally by proprietary software.
Several methods exist for screening children in the preverbal age group. Red reflex testing and cover testing should be carried out at regular intervals, as suggested by the American Academy of Pediatrics.8 Photoscreening and autorefraction are also well-validated techniques for such screening.9,10 VEP screening has had limited validation, but shows promise in detecting amblyopia and other causes of impaired visual acuity in preverbal children; if incorporated into a well-child visit it would thus be most useful in this age group.11 Although these cases do not provide sufficient evidence to justify the use of VEP as the sole screening methodology for pre-verbal children, they do suggest that some form of preschool vision screening of healthy preverbal children should be performed in the medical home.
- Shields CL, Shields JA. Retinoblastoma management: advances in enucleation, intravenous chemoreduction, and intra-arterial chemotherapy. Curr Opin Ophthalmol. 2010;21:203–212. doi:10.1097/ICU.0b013e328338676a [CrossRef]
- Seregard S, Lundell G, Svedberg H, Kivelä T. Incidence of retinoblastoma from 1958 to 1998 in Northern Europe: advantages of birth cohort analysis. Ophthalmology. 2004;111:1228–1232. doi:10.1016/j.ophtha.2003.10.023 [CrossRef]
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- Shields CL, Shields JA. Basic understanding of current classification and management of retinoblastoma. Curr Opin Ophthalmol. 2006;17:228–234. doi:10.1097/01.icu.0000193079.55240.18 [CrossRef]
- United States Preventive Services Task Force. Vision screening for children 1 to 5 years of age: US Preventive Services Task Force Recommendation statement. Pediatrics. 2011;127:340–346.
- Donahue SP, Ruben JB, American Academy of Ophthalmology et al. US Preventive Services Task Force vision screening recommendations. Pediatrics. 2011;127:569–570. doi:10.1542/peds.2011-0020 [CrossRef]
- Shields JA, Shields CL. Intraocular Tumors: A Text And Atlas. Philadelphia: Saunders; 1992:305–332.
- American Academy of Pediatrics, Section on Ophthalmology, American Association for Pediatric Ophthalmology and Strabismus, American Academy of Ophthalmology, American Association of Certified Orthoptists. Red reflex examination in neonates, infants, and children. Pediatrics. 2008;122:1401–1404.
- Rowatt AJ, Donahue SP, Crosby C, Hudson AC, Simon S, Emmons K. Field evaluation of the Welch Allyn SureSight vision screener: incorporating the vision in preschoolers study recommendations. J AAPOS. 2007;11:243–248. doi:10.1016/j.jaapos.2006.09.008 [CrossRef]
- Matta NS, Arnold RW, Singman EL, Silbert DI. Comparison between the plusoptiX and MTI Photoscreeners. Arch Ophthalmol. 2009;127:1591–1595. doi:10.1001/archophthalmol.2009.294 [CrossRef]
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