PEDIATRICS Vol. 104 No. 4
October 1999,
p. e44
ELECTRONIC ARTICLE:
Utility of Pupillary Dilation for Detecting Leukocoria in
Patients With Retinoblastoma
John C. Canzano, MD and
James T. Handa, MD
From the Department of Ophthalmology, University of California,
Davis, Sacramento, California.
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ABSTRACT |
In the United States, 50% of all retinoblastoma
cases are diagnosed after the observation of leukocoria by a family
member or primary care physician. However, leukocoria produced by
retinoblastoma lesions can often be missed by direct ophthalmoscopic
examination through an undilated pupil. The purpose of this study is to
demonstrate the utility of pupillary dilation for the detection of
leukocoria in suspected cases. Seven patients (10 eyes), aged 2 days to
20 months, with retinoblastoma were examined for leukocoria using a
direct ophthalmoscope with the pupils first undilated and then after
pharmacologic dilation with 0.5% cyclopentolate and 2.5% phenylephrine. Leukocoria was detected by direct ophthalmoscopy on
undilated examination in 3 of 10 eyes (30%). In contrast, leukocoria was observed after pupillary dilation in 10 of 10 eyes (100%). The
retinoblastoma lesions, from 2 to 10 mm in diameter, were located
within the posterior 45° of the retina. Pupillary dilation is a safe
and effective tool that can enhance the ability of the examiner to
detect leukocoria. Dilation may afford early diagnosis and treatment,
and therefore should be considered on patients in whom the diagnosis of
retinoblastoma is entertained.
Key words:
direct ophthalmoscope,
leukocoria,
pupillary dilation,
retinoblastoma.
Retinoblastoma, the most common intraocular malignancy of
childhood, occurs in 1 of 20 000 live births with 200 to 300 new cases
reported in the United States per year, and has no sexual or racial
predisposition.1 Caused by a mutation in the retinoblastoma gene, which is located in the long arm of chromosome 13 (13q14), ~94% of newly diagnosed retinoblastoma cases are sporadic whereas only 6% are inherited as a familial tumor.2-4 With a mean age at diagnosis of 12 months for inherited and 18 months
for sporadic cases, retinoblastoma can involve 1 or both eyes, with one
third of all cases having bilateral involvement.5 The
survival rate for patients with retinoblastoma is 92%.6 With such a high survival rate, the incidence of retinoblastoma has
increased, and the likelihood of seeing children with retinoblastoma is
accordingly increased.
The goal of treatment is to save life and, if possible, vision.
Treatment depends on the clinical presentation. Factors such as
bilaterality, size, location, and number of retinoblastoma tumors
influence which treatment modality is selected. A delay in diagnosis
can result in large and/or multiple tumors, which reduces the
possibility of preserving life and vision. In these cases, enucleation
may be the only treatment option. On the other hand, early diagnosis
permits local treatment because the tumors are small. Local treatment
for retinoblastoma such as laser photocoagulation, cryopexy, or
episcleral plaque radiotherapy, is minimally invasive with low
morbidity and high treatment success in which both life and vision are
maintained.7-9 Recently, combination therapy using
chemotherapy with local treatment modalities has been advocated to
salvage vision in advanced cases.10,11
The most common presenting sign in retinoblastoma is leukocoria (white
pupillary reflex), which occurs in 50% to 62% of
cases.12 In a normal eye, if light is directed into the
pupil, the pupillary space will appear as a homogeneous bright
reddish-orange color that is called the red reflex. It is a reflection
of the choroidal vasculature and retinal pigmentation.13
Retinoblastoma, which appears as a white mass overlying or infiltrating
the retina, interrupts the red reflex when light is shined in the eye.
The red reflex is best seen by looking into the pupil with a direct ophthalmoscope. However, it can be difficult to visualize through a
small pupil.
Pediatricians and other primary care physicians usually have the first
opportunity to evaluate a child suspected of having leukocoria.
However, the infant pupillary examination can be difficult and the
detection of leukocoria can be missed despite the presence of a
retinoblastoma lesion, especially in a small pupil. Pharmacologic pupillary dilation can enhance the examiner's ability to detect both
the red reflex and leukocoria. The purpose of this study is to
demonstrate that the detection of leukocoria using direct ophthalmoscopy is enhanced with pupillary dilation.
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METHODS |
Seven consecutive patients in whom the diagnosis of
retinoblastoma was confirmed by ophthalmologic examination,
ultrasonography, and radiologic imaging were examined for the presence
of leukocoria by one ophthalmologist (J.T.H.) with a direct
ophthalmoscope under two conditions. At the time of pupillary
examination, the examiner was masked to the eye and location of tumors.
The patient was held in the lap of the parent to obtain maximum
cooperation. The pupil was visualized through the ocular of a direct
ophthalmoscope that was held at arm's length. With the patient in
primary gaze, the pupillary reflex was examined directly in front of,
and at several different angles to assess the superior, nasal,
inferior, and temporal quadrants of the retina. Leukocoria was defined
as an observed reduction in the red reflex. Testing for leukocoria was
performed first under typical medical office lighting conditions that
maintains the pupils constricted, before pupillary dilation. The
pupillary diameter was measured after 3 seconds of illumination on the
pupil, and the presence or absence of leukocoria was recorded. The
pupils were pharmacologically dilated with 1 drop to each eye twice of
0.5% cyclopentolate and 2.5% phenylephrine. Approximately 30 minutes
later, the pupillary diameter was measured, and the pupillary
examination with a direct ophthalmoscope was repeated with the
examination room lights off. Each pupillary examination lasted ~30
seconds. Retinoblastoma tumors were confirmed using indirect
ophthalmoscopy and detailed retinal drawings of the lesions were made.
Ultrasonography and fundus photography were performed during an
examination under anesthesia to further characterize the extent of
disease.
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RESULTS |
Seven consecutive patients (4 boys and 3 girls) aged 2 days to 20 months (10 eyes) with suspected, and later confirmed, retinoblastoma were included in the study. Four of these patients had bilateral disease of which 1 patient had an enucleation before inclusion in the
study. The average undilated pupillary diameter in a fully illuminated
room was 3 mm. Leukocoria was detected in 3 of 10 eyes (30%) with
retinoblastoma under these conditions. In the remaining 7 eyes, a red
reflex was seen in 1 and an indeterminate reflex (neither leukocoria
nor a red reflex) was seen in 6 eyes. After pupillary dilation, the
average pupillary diameter was 7 mm. Leukocoria was observed with
direct ophthalmoscopic examination of pupils in all 10 eyes (100%; Fig
1).
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Fig. 1.
A, Direct ophthalmoscopic examination of the right eye of patient 7 during an examination under anesthesia. External photograph
demonstrating no leukocoria with undilated pupils. B, External
photograph demonstrating leukocoria after pupillary dilation. Note that
the leukocoria fills the pupil incompletely because of the small size
of the lesion. C, Fundus photograph documenting a 2-mm flat,
retinoblastoma tumor just superior to the optic nerve. Note: the lid
speculum was used for photographic purposes during the examination
under anesthesia, and is not necessary for the pupillary examination in
the awake patient.
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The size of the lesions identified by indirect ophthalmoscopy ranged
from 2 to 10 mm in diameter and they were confined to the posterior
pole (posterior 45°). Figure 2 shows a composite retinal map illustrating the sizes and locations of the
retinoblastoma tumors that elicited leukocoria only after dilated,
direct ophthalmoscopic examination. The 3 eyes that demonstrated leukocoria before pupillary dilation had either large tumors (patient 3, left eye, and patient 4, left eye) or a moderately large tumor in
the macula (patient 7, left eye). The case histories of the 7 patients
are summarized in Table 1.
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Fig. 2.
Composite retinal map drawing of the right and left eyes demonstrating
the relative sizes and locations of retinoblastoma tumors that elicited
leukocoria only after pupillary dilation. The numbers correspond to the
individual patients (see Table 1). The inner circle represents the
equator, the middle circle represents the ora serrata, and the outer
circle represents the region of ciliary processes. The small circle in
the center of the chart represents the optic nerve (1.5-mm diameter).
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DISCUSSION |
In this series of 7 patients (10 eyes) with confirmed
retinoblastoma tumors, which ranged from 2 to 10 mm in diameter,
undilated direct ophthalmoscopic examination elicited leukocoria in
only 3 eyes although it became observable in all eyes after
pharmacologic pupillary dilation. Pupillary dilation enabled us to
observe leukocoria from small retinoblastoma tumors in the posterior
pole, moderately sized lesions located outside of the macula, and a
moderately sized posterior lesion in an uncooperative patient. The
results of this study perhaps reflect the maximal improvement in the
ability to detect leukocoria because the examiner was an
ophthalmologist, and the patients were referred for the suspicion of
retinoblastoma. Although we did not determine the effectiveness of this
technique for the primary care physician, we believe with practice, the primary care physician can become proficient with the pupillary examination just as he or she uses the otoscope to diagnose otitis media.
The size of the pupil has a dramatic impact on the area of retina
evaluated during the direct ophthalmoscopic examination. The amount of
light that passes through the pupil, reflects off the retina, and exits
back through the pupil, depends on the pupillary size. In a small
pupil, the retinal area examined for leukocoria is confined to the
macula because it is aligned with the pupillary axis. With a small
pupil, only tumors that have grown large enough to interrupt the
pupillary axis may be detected as leukocoria. In the undilated state,
we observed leukocoria in patient 3 (left eye) and patient 4 (left eye)
because these tumors were large and had crossed into the pupillary
space. We believe that leukocoria was detected in the undilated pupil
of the left eye in patient 7, not only because of its size, but also in
part, because of the tumor's macular location. Furthermore, in the 7 eyes without obvious leukocoria, we confirmed a red reflex in only 1 eye, which suggests that a small pupil can prevent the observer from
obtaining a quality pupillary examination.
Pupillary dilation improved our ability to observe leukocoria resulting
from small retinoblastoma lesions in the posterior pole and larger
lesions located outside of the posterior pole. Leukocoria was detected
after pupillary dilation in a posteriorly located, isolated tumor as
small as 3 mm (patient 3). Likewise, tumors ranging from 2 to 5 mm in
diameter adjacent to the optic nerve (patients 1, 2, 6, and 7) were
detected after the pupils were dilated. We believe that our ability to
find leukocoria in these patients was enhanced in part, because the
combined size of the optic nerve and retinoblastoma lesions enlarged
the area that blunted the red reflex. Pupillary dilation also improved our ability to observe lesions located outside of the macula. Patients
3 (right eye) and 4 (right eye) had moderately sized tumors located in
the nasal retina. A large pupil allowed us to examine peripheral areas
of the posterior pole.
Patient 5 presented with a moderately large tumor in the posterior pole
that was missed during the undilated pupillary examination, but was
seen after the pupil was dilated. This child, who suffers from
developmental delay, was very uncooperative. As a result, the pupillary
examination was difficult. Pupillary dilation may be especially useful
in situations when patient cooperation is suboptimal, and efficient
testing for leukocoria is essential.
Pupillary dilation can be incorporated into the general pediatric
examination by instilling dilating drops at the beginning of the
appointment. The pupillary examination takes 30 seconds to perform, and
thus, is not time consuming. Because pupillary dilation takes 20 to 30 minutes, the leukocoria check can be performed either at the conclusion
of the general examination or if the pupils are not dilated, after
examining another patient at a later time. This technique has been used
routinely to screen all new patients within the first 6 weeks of life
by the Department of Pediatrics, University of Southern California, and
several large pediatric practices in Los Angeles (personal
communication, Robert Adler, MD, Associate Chair, Department of
Pediatrics, University of Southern California, 1998). Patients to
consider for dilated pupillary examination include those at risk for
retinoblastoma, or patients in whom an abnormal pupillary reflex even
if intermittent, was noted by a family member or caregiver. Besides
retinoblastoma, leukocoria heralds a significant retinal problem such
as astrocytic hamartoma, Coats' disease, ocular toxocariasis, retinal
detachment, retinopathy of prematurity, and vitreous hemorrhage.
Pupillary dilation can be safely and effectively used in the pediatric
population. Adverse effects have been observed in children who have
received phenylephrine and cyclopentolate such as fever, flushing of
the face, tachycardia, hypertension, nausea, and vomiting, but the
incidence is low.14-16 To minimize side effects, a
combination eyedrop such as Cyclomydril (Alcon Laboratories, Inc, Ft
Worth, TX), which contains 0.2% cyclopentolate and 1%
phenylephrine, could be considered because of its low concentrations. Many physicians express concern that pharmacologic pupillary dilation will precipitate acute angle-closure glaucoma. This occurrence is rare
in children.17 We believe that the benefit of making an
early diagnosis of leukocoria with pupillary dilation far outweighs the
risks associated with pupillary dilation.
This study suggests that pupillary dilation can safely and effectively
enhance the examiner's ability to detect leukocoria. Dilated direct
ophthalmoscopic examination can detect retinoblastoma tumors that are
small and in locations that otherwise would be missed until they grow
to a more advanced stage. Prompt early referral to an ophthalmologist
from early diagnosis could save life and sight. We emphasize however,
that a normal pupillary examination after dilation in a patient whose
parent had seen a suspicious pupil does not rule out retinoblastoma or
other retinal pathology. Therefore, referral to an ophthalmologist
should be strongly considered. Finally, this technique may stimulate
heightened awareness among pediatricians and other primary care
physicians of this important clinical sign. We advocate pupillary
dilation to become a routine tool in the armamentarium of pediatricians and primary care physicians confronted with the possible diagnosis of
leukocoria.
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ACKNOWLEDGMENT |
Support for this research was provided by an unrestricted grant
from Research to Prevent Blindness.
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FOOTNOTES |
Received for publication Apr 2, 1998; accepted Apr 15, 1999.
Reprint requests to (J.T.H.) Department of Ophthalmology, UC
Davis Medical Center, 4860 Y St, Suite 2400, Sacramento, CA 95817. E-mail: jthanda{at}ucdavis.edu
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