DOI:10.2214/AJR.07.7022
AJR 2008; 191:S40-S44
© American Roentgen Ray Society
Radiological Reasoning: Leukocoria in a Child
Nadja Kadom1 and
Raymond W. Sze
1 Both authors: Department of Radiology, Children's National Medical Center, 111
Michigan Ave., Washington, DC 20010.
Received June 21, 2007;
accepted after revision July 14, 2007.
Address correspondence to N. Kadom
(nkadom{at}cnmc.org).
Keywords: CT • head and neck • leukocoria • MRI • pediatric imaging
OBJECTIVE
We discuss the CT findings of leukocoria in a child. Leukocoria is an
abnormal white reflection from the retina during ophthalmoscopy.
CONCLUSION
In patients with leukocoria, CT provides important information about the
presence of calcifications, the size of the globes, and the contrast
enhancement pattern that can help narrow the differential considerations.
Case History
A 10-month-old boy presents to his pediatrician for a routine visit. An
abnormal pupillary reflex on the right, noticed by the family in the otherwise
normal child, is brought to the physician's attention. The child's ability to
walk and his coordination are normal, and he has a normal response to visual
stimuli. The patient is then referred to an ophthalmologist, who finds
bilateral leukocoria but normal vision and gaze and normal object tracking.
Orbital CT is ordered for further evaluation.
CT
The contrast-enhanced CT scan of the orbits
(Fig. 1) shows bilateral normal
and symmetric size of the globes. Abnormal tissue densities are present
bilaterally and are partially calcified. Hounsfield unit attenuation shows no
hemorrhage. Regions of soft-tissue density show moderate contrast enhancement.
On the right, multiple soft-tissue masses protrude into the globe with a broad
attachment to the retina and a lentiform shape, such as seen with retinal
detachment. On the left, the globe is completely filled with abnormal tissue.
Lenses, optic nerves, and periorbital fat and muscles are normal. Visualized
brain tissue and bone structures are normal.
Expert Discussion
The clinical history of leukocoria, meaning loss of the normal red retinal
reflex, is nonspecific and can be found in retinoblastoma, Coats' disease,
toxocariasis, optic nerve drusen, retinopathy of prematurity, persistent
hyperplastic primary vitreous (PHPV), and phthisis bulbi, to consider just the
most common diagnoses.
Key findings here are the normal size of the globes and the presence of
calcifications, which are more compatible with retinoblastoma, Coats' disease,
or toxocariasis.
In optic nerve drusen, the globes are also of normal size, but usually
there are only small calcifications at the site of the optic disk and no
contrast-enhancing soft-tissue masses are present
(Fig. 2). Drusen are usually
not yet sufficiently calcified to be detected on CT at the age of 1 year.
Retinopathy of prematurity may be associated with a normal-sized globe or
microphthalmia; however, calcifications are rare. Although retinopathy of
prematurity occurs bilaterally, there is usually marked asymmetry. A history
of premature birth, low birth weight, and prolonged ventilatory support would
be expected for a diagnosis of retinopathy of prematurity.
Phthisis bulbi and PHPV are usually associated with small size of the globe
and are therefore less likely in this patient with normal-sized globes. Also,
PHPV typically does not calcify.
Additional History
The patient was born at term. There is no history or current sign of
infectious disease.
Expert Discussion
Given the additional history of term birth, a diagnosis of retinopathy of
prematurity can be excluded and retinoblastoma, Coats' disease, and
toxocariasis remain the differential considerations.
Ocular toxocariasis is usually unilateral and seen in older children.
Endophthalmitis from nematode infection causes an inflammatory ocular mass on
CT, usually without significant contrast enhancement. Calcifications are
typically not present but when present are more commonly seen in later stages
of the disease. The lack of a history of infectious disease in this patient
makes the diagnosis of acute toxocariasis unlikely; the young age of the
patient and the lack of past medical illness excludes chronic
toxocariasis.
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Fig. 3A —Illustrative companion case, 3-year-old girl with
retinoblastoma. Unenhanced (A) and contrast-enhanced (B) axial
CT scans of orbit shown with Hounsfield units reveal contrast enhancement that
is hard to detect subjectively. Note increase in Hounsfield unit attenuation
from M = 44.27 HU (A) to M = 70.81 HU (B).
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Fig. 3B —Illustrative companion case, 3-year-old girl with
retinoblastoma. Unenhanced (A) and contrast-enhanced (B) axial
CT scans of orbit shown with Hounsfield units reveal contrast enhancement that
is hard to detect subjectively. Note increase in Hounsfield unit attenuation
from M = 44.27 HU (A) to M = 70.81 HU (B).
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Fig. 4A —Illustrative companion case, 3-year-old boy with bilateral
retinoblastoma shown on axial MRI. T2-weighted unenhanced image (A) of
orbit shows dark mass along left lateral retina. Mass enhances on
gadolinium-enhanced T1-weighted image (B). Note globe prosthesis on
right side.
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Fig. 4B —Illustrative companion case, 3-year-old boy with bilateral
retinoblastoma shown on axial MRI. T2-weighted unenhanced image (A) of
orbit shows dark mass along left lateral retina. Mass enhances on
gadolinium-enhanced T1-weighted image (B). Note globe prosthesis on
right side.
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Coats' disease affects predominantly juvenile males and is a primary
retinal telangiectasia that ultimately causes retinal detachment from massive
subretinal exudates. Calcifications are a rare finding in Coats' disease, and
the disease is more frequently unilateral.
Retinoblastoma shows contrast enhancement on CT, although this may be
difficult to identify without actually measuring the attenuation in Hounsfield
units (Fig. 3A,
3B). If the differentiation of
Coats' disease and retinoblastoma cannot be made clinically, then MRI should
be considered. In the setting of retinoblastoma, a contrast-enhancing mass
would be expected on MRI, and no MRI contrast enhancement is expected of the
subretinal exudates of Coats' disease.
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Fig. 6 —Illustrative companion case, 8-year-old girl with bilateral
retinopathy of prematurity. Unenhanced axial CT scan of orbit shows bilateral
microphthalmia, abnormal calcified tissue traversing right globe, and
abnormally increased globe density and absent lens on left.
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Fig. 7A —Illustrative companion case, 10-year-old boy with persistent
primary vitreous. Orbital axial T1-weighted MR image shows right
microphthalmia, retrolental mass lesion, and bright signal of vitreous.
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Thus, based on imaging features of globe size, calcifications, laterality,
and enhancement pattern in conjunction with patient history and demographics,
the most likely diagnosis is bilateral retinoblastoma.
Clinical Management
The patient underwent bone marrow aspiration and lumbar puncturefor
staging, then surgical enucleation of the right eye. Pathology received a
specimen of eyeball with attached optic nerve that showed necrotic tumor with
large calcifications. Tumor cells were undifferentiated round blue cells, and
Homer Wright and Flexner-Wintersteiner rosettes were present, consistent with
a diagnosis of retinoblastoma. The patient underwent 6 months of chemotherapy
with vincristine, etoposide, and carboplatin after surgery. In addition, the
patient underwent laser therapy to the left globe and bilateral cryotherapy to
enhance tumor response to a subsequent chemotherapy cycle. At present the
patient is without recurrence or metastasis.
Expert Commentary
Retinoblastoma most commonly presents with a white pupillary reflex (that
is frequently first discovered on family pictures), which is usually caused by
a rather large central ocular mass. The second most common presenting sign of
retinoblastoma is strabismus, which is explained by tumor in the region of the
macula disrupting the sensory input needed to keep the globes aligned.
Approximately one third of retinoblastoma patients have bilateral disease.
Early diagnosis and treatment of retinoblastoma are crucial for good vision
prognosis and to obviate radio- and chemotherapy
[1]. Generally, the diagnosis
is made by ophthalmologic examination and the tumor is classified according to
the Reese and Ellsworth classification, which relates size and location of
lesions to clinical outcome
[2].
There are two types of retinoblastoma: The nonhereditary type causes
unilateral disease and constitutes about 70% of cases; the hereditary form is
bilateral and occurs in the remaining 30% of patients
[3]. Hereditary retinoblastoma
also occurs in conjunction with midline intracranial masses, usually
pineoblastoma, of either the suprasellar or the pineal region (trilateral
disease) [4], or in both
suprasellar and pineal regions (tetralateral disease)
[5]. The incidence of
trilateral retinoblastoma is reported to be between 1.5% and 5% of patients
with retinoblastoma [4].
Imaging plays a confirmatory role in the diagnostic process but plays a
crucial role in assessing the extent of ocular disease, retrobulbar spread,
and intracranial metastasis
[1]. Sonography can be helpful
in patients younger than 5 years who have media opacity or leukocoria in whom
ophthalmologic examinations are not diagnostic
[1]. It is possible to identify
intraocular calcification, a key feature of retinoblastoma, on sonography, but
the accuracy is only 80%. Sonography provides only limited evaluation for
tumor extension beyond the globe
[6]. In addition, the presence
of complex intraocular interfaces, such as those caused by vitreous opacities,
retinal masses, subretinal fluid, and retinal detachments, limit the value of
sonography [6]. CT is the best
tool for the detection of intraocular calcifications, which are present in
more than 90% of retinoblastoma patients
[1,
5]. Calcium forms as a complex
with DNA that is released from necrotic retinoblastoma cells
[6]. A rare, diffusely
infiltrating form of retinoblastoma usually has no calcifications
[6]. Calcifications are also
rarely seen in extraocular metastatic retinoblastoma
[6]. Size and configuration of
calcifications vary; calcified areas as small as 2 mm are thought to be
reliably detected on CT
[6].
MRI plays a key role in the staging of retinoblastoma because it allows
evaluation for metastasis along the optic pathway and the detection of other
intracranial masses [1,
5]. The specificity of MRI in
diagnosing retinoblastoma is less than that of CT because of the difficulty of
identifying calcifications, which may present with varied degrees of signal
hypointensity on all common pulse sequences
[6]. However, MRI is better for
differentiating retinoblastoma from other similar lesions
[6]. On MRI, retinoblastoma
shows slightly to moderately hyperintense signal on T1- and proton
density–weighted images, as well as low signal intensity on T2-weighted
images [6]
(Fig. 4A). Moderate to marked
contrast enhancement is seen (Fig.
4B). Occasionally, there will be anterior contrast enhancement
(radiologists are not quite sure what this means), making retinoblastoma
difficult to differentiate from PHPV
[6]. With respect to size, the
lower limit for MRI detection of retinoblastoma lesions is considered to be
2–3 mm [6].
Generally, CT is more widely available than MRI and may be a sufficient
confirmatory imaging test in children with leukocoria. However, in patients
with hereditary disease and a chance of trilateral retinoblastoma, as well as
in older patients in whom other simulating lesions are becoming more common,
MRI should be performed during the initial diagnostic process. All patients
with an established diagnosis of retinoblastoma should undergo MRI to evaluate
for extraocular spread of disease
[6].
Leukocoria is also seen in other ocular diseases that cause bloody
opacification of the vitreous, inflammatory exudates, or retinal detachment of
causes other than retinoblastoma. Among these entities, the main differential
diagnoses to be considered for retinoblastoma are Coats' disease and
toxocariasis. These entities have been termed
"pseudoretinoblastoma"
[7] to illustrate the
diagnostic dilemma between these three entities at both ophthalmology
examination and imaging.
Coats' disease also presents with strabismus in addition to leukocoria. Two
thirds of the patients with this disease present before the age of 10 years.
Most commonly the disease is unilateral; bilateral involvement tends to be
asynchronous. Boys are predominantly affected. On ophthalmology examination,
vascular telangiectasias are found; and associated leakage from affected
vessels causes exudates that consist mostly of cholesterol and that ultimately
cause retinal detachment. CT is usually sufficient to differentiate Coats'
disease from retinoblastoma because of the usual absence of calcifications in
Coats' disease (Fig. 5).
However, if CT is inconclusive or if the diagnosis of Coats' disease versus
other ocular disorders is unclear, MRI should be performed. Exudates of Coats'
disease are bright on unenhanced T1-weighted images, and contrast enhancement
may be seen mostly in a linear fashion when retinal detachment is present
[8].
Toxocariasis is a manifestation of infection with second-stage larvae of
the nematode Toxocara canis
[9,
10]. The serum prevalence in
children has been reported to be between 4% and 31% in developed countries and
up to 86% in tropical regions. The disease is usually unilateral and is more
common in older children [10].
Enhanced T1-weighted MR images can show irregular, thick, intravitreal bands
related to endophthalmitis or intraocular abscesses
[10].
Other diseases presenting with leukocoria include retinopathy of
prematurity, PHPV, and phthisis bulbi. Patients with retinopathy of
prematurity have a characteristic history of premature birth, low birth
weight, and having undergone oxygen therapy
[11]. Retinopathy of
prematurity is usually a bilateral disease with abnormal retinal fibrovascular
tissue proliferation extending into the vitreous cavity
(Fig. 6) and causing retinal
detachment [11].
Calcifications located in the lenses, choroid, and retrolental tissue have
been reported in later stages of the disease
[11]. PHPV is typically
unilateral and associated with microphthalmia in a full-term infant
[12]. Histologically, PHPV is
a persistent retrolental fibrovascular membrane in combination with
degeneration of the lens fibers that may ultimately cause a cataract
[12]. Retinal detachment is
often present. Microphthalmia (Fig.
7A) and absence of intraocular calcifications sets this entity
apart from Coats' disease and retinoblastoma, respectively, and can be easily
confirmed on CT [12]. MRI
offers better identification of an abnormal lens, retrolental mass
(Fig. 7B), and associated
retinal and posterior hyaloid detachment. Abnormal contrast enhancement on
T1-weighted images may be seen in the retrolental mass and anterior chamber
[12].
Phthisis bulbi is a generic term to describe a shrunken globe with
extensive intraocular calcifications
[5]. Few cases have been
reported in which retinoblastoma presented with phthisis bulbi in one eye in
combination with buphthalmos of the other eye, the incidence being
2–2.7% [13]. The
mechanism is thought to be an intraocular infarction causing inflammation;
secondary glaucoma may then produce buphthalmos
[13].
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OBJECTIVE
CONCLUSION
