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Ultrasonic Aid in the Evaluation of Leukocoria
ULTRASONIC AID IN T H E EVALUATION O F LEUKOCORIA K. A. GITTER, M.D.,
D. MEYER, M.D.,
G. ORTOLAN, M.D.,
R. H. W H I T E , JR.,
AND L. K.
SARIN,
M.D.,
M.D.
Philadelphia, Pennsylvania
This paper reports the use of time ampli tude ultrasonography (A mode) as a clinical aid in differential diagnosis of Ieukocoria. The three commonest causes of a white pupil are congenital cataract, retinoblastoma, and pseudoglioma. Included under the last category are (1) retrolental fibroplasia; (2) persistence of tunica vasculosa lentis; (3) organization of a vitreous mass, forming a cyclitic membrane; (4) Coats' disease; (5) lar val granulomatosis; (6) exudative retinitis or chorioretinitis, or both; (7) massive reti nal fibrosis (retinal dysplasia) ; (8) other tu mors, such as angiomatosis retinae or diktyoma; and (9) congenital retinal detach ment. Of lifesaving importance is the differ entiation of retinoblastoma from other causes of Ieukocoria. Time-amplitude ultra sonic techniques extend diagnostic capabili ties beyond the limits of ophthalmoscopy, From the Ultrasound Laboratory, Wills Eye Hospital. This study was supported in part by grants from Fight for Sight of the National Coun cil to Combat Blindness, and training grant MB5076 from the National Institute of Neurological Diseases and Blindness, National Institutes of Health.
transillumination, study.
X-ray, and
fluorescein
MATERIALS AND METHODS
Twenty-five patients with Ieukocoria were examined by ultrasound between October 1965 and March 1967 at Wills Eye Hospital. All examinations, except for three older children, were performed under general anesthesia using fluothane inhalation. Pupils were widely dilated for binocular, indirect ophthalmoscopy with scleral indentation. Ul trasound examination was then performed by placing the transducer face on the anes thetized cornea of each eye, using 0.5% methylcellulose as a coupling medium. The acoustic beam was directed through the lens along the optical axis to obtain bulbar axial length measurements accurate to within 1.0 mm (fig. 1). The globe was subsequently probed in all quadrants by placing the trans ducer perpendicular to the sclera in exposed portions to determine the location and con figuration of any abnormal echoes in the posterior segment.* ♦Smith Kline Instrument Company, Echoline 12 and 20 instruments
Fig. 1 (Gitter, Meyer, White, Ortolan, & Sarin). Normal echogram showing anterior lens capsule (A), posterior lens capsule (B), and posterior bulbar wall (C) echoes. All echoes following (C) represent normal retrobulbar echoes (D). The vitreous cavity (from B to C) is acoustically silent.
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Table 1 demonstrates the various clinical entities comprising these 25 patients with TABLE 1 DIFFERENTIAL DIAGNOSES OF WHITE PUPIL WITH ULTRASONOGRAPHY
Retinoblastoma Congenital cataract Retrolental fibroplasia _ Persistent primary hyperplastic vitreous Uveitis with detachment Incontinentia pigmenti Total
5 4 7 5 3 1 25
Fig. 3 (Gitter, Meyer, White, Ortolan, & Sarin). External eye photograph of a two-year-old patient with leukocoria and hypopyon of the anterior chamber.
leukocoria. All five patients with histologically confirmed retinoblastoma demonstrated typical tumor-type echogram patterns with dense, irregular echoes arising from the an terior tumor surface and extending to the posterior bulbar wall (fig. 2). In one patient the entire fundus view was precluded due to an anterior chamber hypopyon secondary to retinoblastoma infiltration (fig. 3). Ultra sound revealed irregular echoes extending throughout the vitreous cavity (fig. 4). Although congenital cataracts offer little confusion in differential diagnosis, the pres ence of an echo-free posterior segment can exclude other etiologic considerations, such as persistent hyperplastic primary vitreous with posterior subcapsular cataracts. All four patients with congenital cataracts dem onstrated clear, normal echograms showing
^
INK
Fig. 2 (Gitter, Meyer, White, Ortolan, & Sarin). External eye photograph of patient with leukocoria due to retinoblastoma. Echogram demonstrates tumor pattern; a = anterior wall of tumor, x = echos arising from tumor, and b = posterior bulbar wall. Also, note axial length is 23 mm, equal to normal fellow eye.
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FEBRUARY, 1968
Fig. 4 (Gitter, Meyer, White, Ortolan, & Sarin). Upper echogram. tracing reveals abnormal irregular echoes throughout the vitreous cavity interpreted as a tumor pattern. The enucleated sec tion reveals a necrotic retinoblastoma (correlates with Figure 3).
anterior and posterior lens capsule echoes followed by a clear vitreous space. Each of seven patients with retrolental fibroplasia demonstrated microphthalmos (four of marked degree) as a prime ultra sonic finding (fig. 5). Additionally, five of these patients showed retrolental echoes (im mediately behind the normal posterior lens capsule echo) (fig. 6 ) , and retinal detach ment type echoes in the posterior segment. In two patients with known retrolental fibroplasia, microphthalmos with an abnormal ret rolental echo and an otherwise normal pos terior segment was found.
Fig. S (Gitter, Meyer, White, Ortolan, & Sarin). RLF patient displaying leukocoria and band keratophaphy O.D. and fundus pic ture of characteristic "dragged disc" O.S. The echogram shows 18 mm microphthalmos of right eye, compared to 24 mm of left eye. Note the retinal detachment echo (A) in the right eye.
There were five patients with persistent hyperplastic primary vitreous and each was shown to have microphthalmos of mild de gree (3 mm or less) by axial ultrasonic measurements. Four of five patients also re vealed an abnormal retrolental echo (fig. 7). In three of the five patients the posterior seg ment was otherwise acoustically clear, whereas in the remaining two, retinal de tachment type echoes were found. Figure 8 demonstrates the ultrasound pattern ob tained in an 11-month-old boy with leukocoria due to persistent hyperplastic primary vit reous. Histologic sections (fig. 9) revealed a
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1M
Fig. 6 (Gitter, Meyer, White, Ortolan, & Sarin). Echogram of microphthalmic eye with retrolental fibroplasia RLF measuring 12-13 mm (on 15 mm scale). A = pos terior lens capsule; R = abnormal retrolental echo, and P = posterior bulbar wall echo.
retrolental membrane, retinal detachment, and hyaloid remnants. Axial measurements indicated a 2-3 mm shortening of the in
volved eye compared to the normal fellow eye, although clinical microphthalmos was not evident. In all three patients with uveitis and de tachment, the clinical picture was that of occlusio pupillae with iris bombe. These pa tients demonstrated microphthalmos and de tachment-type echoes in the posterior seg ment. Clinically, microphthalmos in these in dividuals represented early phthisis of the globe secondary to long-standing uveitis. A single case of incontinentia pigmenti demon strated microphthalmos by axial ultrasonic length measurements as well as an abnormal retrolental echo. DISCUSSION
Time amplitude ultrasound can detect changes in bulbar dimensions otherwise clin-
Fig. 7 (Gitter, Meyer, White, Ortolan, & Sarin). Patient with persistent hyperplastic primary vitreous in O.S. and normal O.D. Echogram reveals normal O.D. and slight microphthalmos O.S. as seen by comparing the linear distances of the posterior bul bar wall echoes (P). Also note the small, abnormal retrolental echo (R) in O.S.
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FEBRUARY, 1968
Fig. 8 (Gitter, Meyer, White, Ortolan, & Sarin). Echogram of microphthalmic eye (17-18 mm) in proven PHPV—see Figure 9. Note the presence of a retinal detach ment echo (R) and the absence of tumor echoes between (R) and (P), the posterior bulbar wall.
ically indiscernible. Even where ultrasound revealed 3 mm of axial shortening, clinical detection of microphthalmos was difficult or impossible. Retinoblastomas have never been reported arising in congenitally microphthal mic eyes, whereas the more frequent forms of pseudoglioma (retrolental fibroplasia and persistent hyperplastic primary vitreous) are almost always associated with some degree of microphthalmos.1"3 Thus, axial length mea surements assume major clinical significance. The configuration and amplitude of ab normal posterior segment echoes, in addition to axial length determination, help differ entiate pseudogliomas from retinoblastomas. Oksala* mentioned the use of ultrasound in the differential diagnosis of patients with ret rolental fibroplasia versus retinoblastoma. Like any other solid intraocular neoplasm, retinoblastomas produce irregular, nonhomogeneous amplitude emanating from the an
terior tumor surface and continuing to the posterior bulbar wall. This echogram pattern is similar to other solid detachments, choroidal hemorrhages, organized subretinal hem orrhages, and Coats' disease with exuda tive detachments.5 Howard and Ellsworth 8 showed that in 50% of 265 patients with suspected retino blastoma, the actual diagnosis proved to be congenital cataract, persistent hyperplastic primary vitreous, or retrolental fibroplasia. In our series of 25 leukocoria patients, these diagnoses were found in 64%. The ultra sound pattern in all these patients revealed a nontumor echogram pattern with absence of irregular echoes throughout the vitreous space. It is essential to realize that A-scan ultrasound cannot differentiate between the various pseudogliomas, but can help differ entiate this group from the formidable reti noblastoma.
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with leukocoria, ultrasound affords another diagnostic tool and has now become a rou tine examining procedure for patients with leukocoria at Wills Eye Hospital. SUMMARY
1. Ultrasound is useful in determining clinically indiscernible microphthalmos, which aids the clinical diagnostic evaluation of leukocoria 2. Retinoblastomas produce tumor-type echograms similar to other solid detachments. 3. Retrolental fibroplasia and persistent hyperplastic primary vitreous are character ized by microphthalmos with or without a retinal detachment and no evidence of a tu mor-type echogram. 4. Congenital cataracts do not produce ab normal echoes of the posterior segment. 1601 Spring Garden Street (18130) ACKNOWLEDGMENT
We wish to thank Mr. Johnny Justice, medical photographer, for his assistance. REFERENCES
Fig. 9 (Gitter, Meyer, White, Ortolan, & Sarin). Photography of external eye showing leukocoria in patient with PHPV. Histologic section revealed a retrolental membrane, retinal detachment, and hy aloid remnants of PHPV. See echogram (fig. 8).
Although clinical acumen remains the most important factor in evaluating patients
1. Von Hippel, E.: Handbuch der speziellen pathologischen anatomie und histologie. Berlin, Springer-Verlag, vol. 2, pt. 2, 1931. 2. Reese, A. B.: Persistent hyperplastic primary vitreous. Am. J. Ophth. 40:317, 1955. 3. Manshot, W. A.: Persistent hyperplastic pri mary vitreous. Arch. Ophth. 59:188, 1958. 4. Oksala, A.: The clinical value of time-ampli tude ultrasonography. Am. J. Ophth. 57:453, 1964. 5. Gitter, K. A., Meyer, D., Sarin, L. K.: The use of ultrasound to evaluate in the diagnosis of eyes with opaque media. Am. J. Ophth. 64:100, 1967. 6. Howard, G. H. and Ellsworth, R. M.: Differ ential diagnosis of retinoblastoma. A statistical sur vey of 500 children. I. Relative frequency of the le sions which simulate retinoblastoma. Am. J. Ophth. 60:610, 1965.
D. MEYER, M.D.,
G. ORTOLAN, M.D.,
R. H. W H I T E , JR.,
AND L. K.
SARIN,
M.D.,
M.D.
Philadelphia, Pennsylvania
This paper reports the use of time ampli tude ultrasonography (A mode) as a clinical aid in differential diagnosis of Ieukocoria. The three commonest causes of a white pupil are congenital cataract, retinoblastoma, and pseudoglioma. Included under the last category are (1) retrolental fibroplasia; (2) persistence of tunica vasculosa lentis; (3) organization of a vitreous mass, forming a cyclitic membrane; (4) Coats' disease; (5) lar val granulomatosis; (6) exudative retinitis or chorioretinitis, or both; (7) massive reti nal fibrosis (retinal dysplasia) ; (8) other tu mors, such as angiomatosis retinae or diktyoma; and (9) congenital retinal detach ment. Of lifesaving importance is the differ entiation of retinoblastoma from other causes of Ieukocoria. Time-amplitude ultra sonic techniques extend diagnostic capabili ties beyond the limits of ophthalmoscopy, From the Ultrasound Laboratory, Wills Eye Hospital. This study was supported in part by grants from Fight for Sight of the National Coun cil to Combat Blindness, and training grant MB5076 from the National Institute of Neurological Diseases and Blindness, National Institutes of Health.
transillumination, study.
X-ray, and
fluorescein
MATERIALS AND METHODS
Twenty-five patients with Ieukocoria were examined by ultrasound between October 1965 and March 1967 at Wills Eye Hospital. All examinations, except for three older children, were performed under general anesthesia using fluothane inhalation. Pupils were widely dilated for binocular, indirect ophthalmoscopy with scleral indentation. Ul trasound examination was then performed by placing the transducer face on the anes thetized cornea of each eye, using 0.5% methylcellulose as a coupling medium. The acoustic beam was directed through the lens along the optical axis to obtain bulbar axial length measurements accurate to within 1.0 mm (fig. 1). The globe was subsequently probed in all quadrants by placing the trans ducer perpendicular to the sclera in exposed portions to determine the location and con figuration of any abnormal echoes in the posterior segment.* ♦Smith Kline Instrument Company, Echoline 12 and 20 instruments
Fig. 1 (Gitter, Meyer, White, Ortolan, & Sarin). Normal echogram showing anterior lens capsule (A), posterior lens capsule (B), and posterior bulbar wall (C) echoes. All echoes following (C) represent normal retrobulbar echoes (D). The vitreous cavity (from B to C) is acoustically silent.
190
VOL. 65, NO.
ULTRASONIC AID IN LEUKOCORIA RESULTS
Table 1 demonstrates the various clinical entities comprising these 25 patients with TABLE 1 DIFFERENTIAL DIAGNOSES OF WHITE PUPIL WITH ULTRASONOGRAPHY
Retinoblastoma Congenital cataract Retrolental fibroplasia _ Persistent primary hyperplastic vitreous Uveitis with detachment Incontinentia pigmenti Total
5 4 7 5 3 1 25
Fig. 3 (Gitter, Meyer, White, Ortolan, & Sarin). External eye photograph of a two-year-old patient with leukocoria and hypopyon of the anterior chamber.
leukocoria. All five patients with histologically confirmed retinoblastoma demonstrated typical tumor-type echogram patterns with dense, irregular echoes arising from the an terior tumor surface and extending to the posterior bulbar wall (fig. 2). In one patient the entire fundus view was precluded due to an anterior chamber hypopyon secondary to retinoblastoma infiltration (fig. 3). Ultra sound revealed irregular echoes extending throughout the vitreous cavity (fig. 4). Although congenital cataracts offer little confusion in differential diagnosis, the pres ence of an echo-free posterior segment can exclude other etiologic considerations, such as persistent hyperplastic primary vitreous with posterior subcapsular cataracts. All four patients with congenital cataracts dem onstrated clear, normal echograms showing
^
INK
Fig. 2 (Gitter, Meyer, White, Ortolan, & Sarin). External eye photograph of patient with leukocoria due to retinoblastoma. Echogram demonstrates tumor pattern; a = anterior wall of tumor, x = echos arising from tumor, and b = posterior bulbar wall. Also, note axial length is 23 mm, equal to normal fellow eye.
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AMERICAN JOURNAL OF OPHTHALMOLOGY
FEBRUARY, 1968
Fig. 4 (Gitter, Meyer, White, Ortolan, & Sarin). Upper echogram. tracing reveals abnormal irregular echoes throughout the vitreous cavity interpreted as a tumor pattern. The enucleated sec tion reveals a necrotic retinoblastoma (correlates with Figure 3).
anterior and posterior lens capsule echoes followed by a clear vitreous space. Each of seven patients with retrolental fibroplasia demonstrated microphthalmos (four of marked degree) as a prime ultra sonic finding (fig. 5). Additionally, five of these patients showed retrolental echoes (im mediately behind the normal posterior lens capsule echo) (fig. 6 ) , and retinal detach ment type echoes in the posterior segment. In two patients with known retrolental fibroplasia, microphthalmos with an abnormal ret rolental echo and an otherwise normal pos terior segment was found.
Fig. S (Gitter, Meyer, White, Ortolan, & Sarin). RLF patient displaying leukocoria and band keratophaphy O.D. and fundus pic ture of characteristic "dragged disc" O.S. The echogram shows 18 mm microphthalmos of right eye, compared to 24 mm of left eye. Note the retinal detachment echo (A) in the right eye.
There were five patients with persistent hyperplastic primary vitreous and each was shown to have microphthalmos of mild de gree (3 mm or less) by axial ultrasonic measurements. Four of five patients also re vealed an abnormal retrolental echo (fig. 7). In three of the five patients the posterior seg ment was otherwise acoustically clear, whereas in the remaining two, retinal de tachment type echoes were found. Figure 8 demonstrates the ultrasound pattern ob tained in an 11-month-old boy with leukocoria due to persistent hyperplastic primary vit reous. Histologic sections (fig. 9) revealed a
VOL. 65, NO. 2
ULTRASONIC AID IN LEUKOCORIA
1M
Fig. 6 (Gitter, Meyer, White, Ortolan, & Sarin). Echogram of microphthalmic eye with retrolental fibroplasia RLF measuring 12-13 mm (on 15 mm scale). A = pos terior lens capsule; R = abnormal retrolental echo, and P = posterior bulbar wall echo.
retrolental membrane, retinal detachment, and hyaloid remnants. Axial measurements indicated a 2-3 mm shortening of the in
volved eye compared to the normal fellow eye, although clinical microphthalmos was not evident. In all three patients with uveitis and de tachment, the clinical picture was that of occlusio pupillae with iris bombe. These pa tients demonstrated microphthalmos and de tachment-type echoes in the posterior seg ment. Clinically, microphthalmos in these in dividuals represented early phthisis of the globe secondary to long-standing uveitis. A single case of incontinentia pigmenti demon strated microphthalmos by axial ultrasonic length measurements as well as an abnormal retrolental echo. DISCUSSION
Time amplitude ultrasound can detect changes in bulbar dimensions otherwise clin-
Fig. 7 (Gitter, Meyer, White, Ortolan, & Sarin). Patient with persistent hyperplastic primary vitreous in O.S. and normal O.D. Echogram reveals normal O.D. and slight microphthalmos O.S. as seen by comparing the linear distances of the posterior bul bar wall echoes (P). Also note the small, abnormal retrolental echo (R) in O.S.
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AMERICAN JOURNAL OF OPHTHALMOLOGY
FEBRUARY, 1968
Fig. 8 (Gitter, Meyer, White, Ortolan, & Sarin). Echogram of microphthalmic eye (17-18 mm) in proven PHPV—see Figure 9. Note the presence of a retinal detach ment echo (R) and the absence of tumor echoes between (R) and (P), the posterior bulbar wall.
ically indiscernible. Even where ultrasound revealed 3 mm of axial shortening, clinical detection of microphthalmos was difficult or impossible. Retinoblastomas have never been reported arising in congenitally microphthal mic eyes, whereas the more frequent forms of pseudoglioma (retrolental fibroplasia and persistent hyperplastic primary vitreous) are almost always associated with some degree of microphthalmos.1"3 Thus, axial length mea surements assume major clinical significance. The configuration and amplitude of ab normal posterior segment echoes, in addition to axial length determination, help differ entiate pseudogliomas from retinoblastomas. Oksala* mentioned the use of ultrasound in the differential diagnosis of patients with ret rolental fibroplasia versus retinoblastoma. Like any other solid intraocular neoplasm, retinoblastomas produce irregular, nonhomogeneous amplitude emanating from the an
terior tumor surface and continuing to the posterior bulbar wall. This echogram pattern is similar to other solid detachments, choroidal hemorrhages, organized subretinal hem orrhages, and Coats' disease with exuda tive detachments.5 Howard and Ellsworth 8 showed that in 50% of 265 patients with suspected retino blastoma, the actual diagnosis proved to be congenital cataract, persistent hyperplastic primary vitreous, or retrolental fibroplasia. In our series of 25 leukocoria patients, these diagnoses were found in 64%. The ultra sound pattern in all these patients revealed a nontumor echogram pattern with absence of irregular echoes throughout the vitreous space. It is essential to realize that A-scan ultrasound cannot differentiate between the various pseudogliomas, but can help differ entiate this group from the formidable reti noblastoma.
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with leukocoria, ultrasound affords another diagnostic tool and has now become a rou tine examining procedure for patients with leukocoria at Wills Eye Hospital. SUMMARY
1. Ultrasound is useful in determining clinically indiscernible microphthalmos, which aids the clinical diagnostic evaluation of leukocoria 2. Retinoblastomas produce tumor-type echograms similar to other solid detachments. 3. Retrolental fibroplasia and persistent hyperplastic primary vitreous are character ized by microphthalmos with or without a retinal detachment and no evidence of a tu mor-type echogram. 4. Congenital cataracts do not produce ab normal echoes of the posterior segment. 1601 Spring Garden Street (18130) ACKNOWLEDGMENT
We wish to thank Mr. Johnny Justice, medical photographer, for his assistance. REFERENCES
Fig. 9 (Gitter, Meyer, White, Ortolan, & Sarin). Photography of external eye showing leukocoria in patient with PHPV. Histologic section revealed a retrolental membrane, retinal detachment, and hy aloid remnants of PHPV. See echogram (fig. 8).
Although clinical acumen remains the most important factor in evaluating patients
1. Von Hippel, E.: Handbuch der speziellen pathologischen anatomie und histologie. Berlin, Springer-Verlag, vol. 2, pt. 2, 1931. 2. Reese, A. B.: Persistent hyperplastic primary vitreous. Am. J. Ophth. 40:317, 1955. 3. Manshot, W. A.: Persistent hyperplastic pri mary vitreous. Arch. Ophth. 59:188, 1958. 4. Oksala, A.: The clinical value of time-ampli tude ultrasonography. Am. J. Ophth. 57:453, 1964. 5. Gitter, K. A., Meyer, D., Sarin, L. K.: The use of ultrasound to evaluate in the diagnosis of eyes with opaque media. Am. J. Ophth. 64:100, 1967. 6. Howard, G. H. and Ellsworth, R. M.: Differ ential diagnosis of retinoblastoma. A statistical sur vey of 500 children. I. Relative frequency of the le sions which simulate retinoblastoma. Am. J. Ophth. 60:610, 1965.