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Photodynamic Therapy for Choroidal Hemangioma Associated With Serous Retinal Detachment
Dennis M. Robertson, MD
Arch Ophthalmol. 2002;120:1155-1161.
ABSTRACT
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Objective To describe the clinical findings in 3 eyes with circumscribed choroidal
hemangioma before and after treatment with photodynamic therapy.
Patients and Methods In the setting of a tertiary referral center, 2 patients with circumscribed,
posteriorly located, choroidal hemangiomas (thicknesses 2.4 and 2.9 mm) contiguous
with the superior boundary of the optic nerve and accompanied by serous detachments
of the sensory retina extending into the macula were treated with photodynamic
therapy using a Zeiss diode laser (692 nm) and a sensitizing dye, verteporfin.
A third patient with a circumscribed subfoveal hemangioma (3.9 mm in thickness)
and a prominent serous retinal detachment was similarly treated. The tumors
were studied with ultrasonography and fluorescein angiography. Visual fields
were tested with Goldmann perimetry at follow-up.
Results Following photodynamic therapy, the serous retinal detachments resolved,
and the choroidal hemangioma in each of the 3 eyes regressed to a nonmeasurable
thickness within 2 to 5 months. The visual acuity improved from 20/50 to 20/20,
20/150 to 20/20, and 3/200 to 20/200 in the respective cases. Two eyes were
treated twice. The tumors have not recurred at follow-up visits from 11 to
16 months. Nerve fiber bundle field defects were not demonstrated with Goldmann
field testing.
Conclusions Photodynamic therapy seems to be effective in the management of circumscribed
choroidal hemangioma. Following photodynamic therapy, the choroidal hemangiomas
in 3 eyes were no longer measurable by ultrasonography, and the accompanying
serous detachments resolved with improvement in the central visual acuities.
Nerve fiber bundle defects were not identified.
INTRODUCTION
INTRAOCULAR CHOROIDAL hemangiomas are benign tumors that, because of
location, growth, and the accompaniment of subretinal fluid, may cause symptoms.
Ordinarily choroidal hemangiomas have not been treated unless there is either
a threatened effect on central vision or an actual effect on central vision
from a secondary exudative retinal detachment. Any treatment for choroidal
hemangioma ideally should cause a resorption of the subretinal fluid and a
regression of the tumor with little collateral damage. This report describes
the clinical findings in 3 eyes with circumscribed choroidal hemangioma before
and after treatment with photodynamic therapy (PDT).
REPORT OF CASES
CASE 1
A 62-year-old man had a 2-week history of decreased visual acuity in
the right eye. He was referred to the Eye Department of the Mayo Clinic, Rochester,
Minn, for a second opinion because he had been seen elsewhere and had been
advised that his right eye harbored what appeared to be a malignant melanoma.
The ophthalmic examination showed a best-corrected visual acuity of
20/50 OD and 20/20 OS. The fundus of the left eye was normal. The fundus of
the right eye showed a 7.5 x 4.0-mm, red-orange choroidal lesion that
was contiguous with the optic nerve from approximately the 10-o'clock position
clockwise to the 2-o'clock position (Figure
1A). The tumor was not intrinsically pigmented, but some lipofuscin
was present on its surface; there was a serous detachment of the sensory retina
that extended from the tumor into the macular area and the nasal fundus. There
was no evidence of a cutaneous hemangioma.
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Figure 1. Case 1. A, A red-orange choroidal
lesion contiguous with the optic nerve from the 10-o'clock position clockwise
to the 2-o'clock position with poorly defined basal boundaries. A serous detachment
extended into the macula. The tumor thickness was 2.4 mm. B, Fluorescein angiography
showing patchy hyperfluorescence at the time retinal arterial flow was well
defined. C, Fluorescein angiography showing late patchy staining of the tumor
with some dye leakage into the subretinal space. D, B-scan ultrasonography
showing a solid dome-shaped lesion 2.9 mm in thickness. This had high internal
reflectivity consistent with a clinical impression of choroidal hemangioma
that was demonstrated with A-scan echography.
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A clinical diagnosis of circumscribed choroidal hemangioma with an exudative
detachment was made. A fluorescein angiogram showed a prearterial flush and
patchy hyperfluorescence at the time the retinal arterial flow was well defined
(Figure 1B). There was late patchy
staining of the tumor with some dye leakage into the subretinal space (Figure 1C).
B-scan ultrasonography showed a solid dome-shaped lesion involving the
choroid (Figure 1D). Standardized
A-scan ultrasonography demonstrated moderate elevation (2.4 mm) and high internal
reflectivity, findings consistent with the clinical impression of choroidal
hemangioma.
Management options that were discussed with the patient included observation,
brachytherapy, transpupillary thermotherapy (TTT), and photodynamic therapy
(PDT). Photodynamic therapy was chosen and administered on November 7, 2000,
using a modified PDT protocol. A pretreatment sketch outlining the hemangioma
and the retinal vessels was prepared to help define landmarks during the laser
treatment (Figure 2A). Ten minutes
after infusing 6 mg/m2 of verteporfin, 3 overlapping laser applications
(laser spot sizes of 4000 µm) were directed to the tumor. Each application
was delivered by the Zeiss laser (692 nm), using a power calculated to be
50 joules/cm2 at an intensity of 600 mW/cm2 over an
interval of 83 seconds. The 4000-µm spot size appeared adequate to encompass
the vertical dimension of the tumor. The first application was directed toward
the more temporal part of the tumor; immediately following this application,
a second application to the more central part of the tumor was delivered,
and a third application was finally directed to the more nasal portion of
the tumor; the central application overlapped the nasal and temporal applications
by approximately 1000 to 1500 µm (Figure
2B). There was no change in the clinical appearance of the retina,
the retinal vasculature, or the tumor immediately after administering the
laser treatment.
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Figure 2. Case 1. A, Sketch showing the
boundaries of the choroidal hemangioma and the subretinal fluid that has extended
into the macula. B, The overlapping circles depict the relative distribution
of the laser applications after the infusion of verteporfin.
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At a follow-up visit 6 weeks after PDT, visual acuity had improved to
20/30+ OD. B-scan ultrasonography at this time showed a reduction in the thickness
of the tumor to approximately half its original thickness. Although there
was no subretinal fluid recognized in the fovea, additional PDT was given.
Four exposures (4000 µm in diameter) were used, with the first 3 exposures
identical to those given previously, and a fourth exposure overlapping the
superior boundaries of the first, second, and third exposures.
The patient returned 3 months later with a visual acuity of 20/20 OD.
There was no subretinal fluid, and the tumor was no longer detectable clinically
or by ultrasonography. There was subtle evidence of subretinal fibrosis, but
the primary ophthalmoscopic appearance was rarefaction of the pigment epithelium
at the site occupied by the original tumor (Figure 3). There was no recurrence of the tumor at a follow-up visit
14 months later. Perimetric fields using a Goldmann perimeter showed no peripheral
field defects.
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Figure 3. Case 1. A, Fundus appearance 3
months following photodynamic therapy with some rarefaction of pigment epithelium
and subtle evidence of subretinal fibrosis. B, The ultrasonographic view of
the same site shown in Figure 2 showing regression of the tumor to a nonmeasurable
thickness.
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CASE 2
A 46-year-old man was seen in the Eye Department of the Mayo Clinic
with a 1-week history of photopsias (flickering lights) and decreased visual
acuity in the left eye. His general health was satisfactory; he was receiving
no medication.
The best-corrected visual acuity was 20/20 OD and 20/150 OS. The pupils
were equal; there was no afferent defect. The right fundus was normal. The
left fundus showed an elevated orange-red choroidal tumor with some lipofuscin
on its surface. There was no recognizable intrinsic pigmentation. The tumor
measured 7 x 7.5 mm in base dimension and was contiguous with the superior
120° of the optic disc (Figure 4A).
There was a serous detachment of the sensory retina that extended from the
tumor into the macula. The clinical diagnosis was a circumscribed choroidal
hemangioma. There was no evidence of a skin hemangioma. A fluorescein angiogram
showed a prearterial patchy filling of the tumor with late patchy staining
and dye leakage into the subretinal space, consistent with the clinical impression
of choroidal hemangioma (Figure 4B).
B-scan ultrasonography showed a solid dome-shaped tumor and a secondary retinal
detachment (Figure 4C); standardized
A-scan echography demonstrated a tumor thickness of 2.9 mm and high internal
reflectivity consistent with the clinical impression of choroidal hemangioma.
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Figure 4. Case 2. A, Choroidal hemangioma
located superior to the optic disc measuring 7 x 7.5 mm in base dimension
and 2.9 mm in thickness. B, Fluorescein angiogram showing the patchy hyperfluorescence
within the tumor at the early arterial phase of angiography. C, B-scan ultrasonography
showing a dome-shaped tumor with a secondary retinal detachment. A-scan echography
demonstrated high internal reflectivity and a tumor thickness of 2.9 mm.
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Options in management were discussed with the patient. The patient chose
to proceed with PDT. Ten minutes after infusing 6 mg/m2 of verteporfin,
6 overlapping 83-second laser applications (laser spot sizes of 5400 µm)
were directed to the tumor using the same power and intensity as described
for patient 1. The first application overlapped the nasal perimeter of the
tumor adjacent to the nasal edge of the disc. The second application was slightly
temporal overlapping the first, and the third was located further slightly
temporally overlapping the second. The fourth, fifth, and sixth applications
were administered more superiorly, overlapping each other and overlapping
the first 3 by approximately 2000 µm (Figure 5). There was no change in the clinical appearance of the
retina, the retinal vasculature, or the tumor immediately after the laser
treatment. No adverse symptoms occurred at the time of the treatment or the
following day as determined by a telephone call. When the patient returned
1 month later, the tumor measured 1.8 mm in maximum thickness, there was decreased
fluid under the retina, and the visual acuity had improved to 20/60 OS. No
additional treatment was given.
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Figure 5. Case 2. Sketch showing the outline
of the choroidal hemangioma, the extension of the exudative detachment through
the macula, and the relative locations of the overlapping laser application
following the infusion of verteporfin.
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Four months later (5 months after the single session of PDT), the visual
acuity measured 20/20 OS. There was no visible tumor by ophthalmoscopy (Figure 6A), biomicroscopy, or ultrasonography
(Figure 6B). There was pigment rarefaction
and some granularity of the retinal pigment epithelium in the area occupied
by the original tumor along with some delicate subretinal fibrosis. A fluorescein
angiogram showed a choroidal vascular pattern superior to the disc where the
pigment in the pigment epithelium was rarefied; more temporally there was
some late hyperfluorescence from dye accumulating in the region of the subretinal
fibrosis.
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Figure 6. Case 2. A, Posttreatment photographs
showing site of tumor that is characterized by a mild hyperpigmentation peripheral
to the central zone where there is marked depigmentation. B, Ultrasonography
shows no measurable tumor at the same relative site shown in Figure 5D.
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There was no recurrence of the tumor at a 13-month follow-up visit.
A formal Goldmann visual field showed no evidence of a peripheral field defect
to suggest nerve fiber bundle damage.
CASE 3
A 67-year-old man was initially seen in the Eye Department of the Mayo
Clinic in 1996 at the age of 62 years because of a posteriorly located submacular
choroidal lesion that had caused a reduction in the visual acuity in his left
eye. Ophthalmic examination documented a visual acuity of 20/20 OD and 20/100
OS. Intraocular tensions were 18 mm by applanation tonometry. There was no
evidence of a skin hemangioma. The anterior segments showed early nuclear
sclerosis in each lens. There were some drusen in the right macula. In the
left eye there was a red-orange lesion in the subfoveal area, overlying lipofuscin
deposits; there was some subtle pigmentation involving the superficial parts
of the tumor. There was no subretinal fluid. The clinical diagnosis was choroidal
hemangioma. B-scan ultrasonography showed a solid dome-shaped lesion; standardized
A-scan echography demonstrated high internal reflectivity consistent with
choroidal hemangioma. The tumor was 3.2 mm thick. A fluorescein angiogram
revealed an early prearterial patchy hyperfluorescence and patchy late staining
of the tumor compatible with the clinical diagnosis of choroidal hemangioma.
Observation was recommended.
The patient returned for follow-up on several occasions between 1996
and 2000. Cystoid macular edema developed over the tumor in 1997, and by 1999,
the thickness of the tumor increased to 3.9 mm. In 2000, the patient noted
an enlarging central blind spot and the visual acuity worsened to 3/200 OS.
A prominent serous detachment of an edematous neurosensory retina was visible
(Figure 7A). B-scan ultrasonography
demonstrated the serous detachment of the sensory retina overlying the hemangioma
that had a thickness of 3.9 mm (Figure 7B).
A-scan echography demonstrated high internal reflectivity. The choroidal hemangioma
was contiguous with the superior and temporal boundary of the optic nerve
for approximately 4 clock hours and had a base dimension estimated to be 9
x 8 mm. Photodynamic therapy was recommended and given in 2001 after
infusing 6 mg/m2 of verteporfin. Four overlapping laser applications
(spot size, 5500 µm) were directed to the tumor to cover its entire
surface (Figure 8). The power was
calculated to be 50 joules/cm2 at an intensity of 600 mW/cm2 over an 83-second interval. The patient returned 2 months later and
noted improvement in his visual acuity (20/200 OS) and a reduction in the
size of the central scotoma. The serous detachment of the sensory retina had
resolved, and the tumor was barely discernible (Figure 9A). Additional treatment was given for residual tumor using
3 overlapping laser applications with spot sizes of 5400 µm. At follow-up
6 weeks later, the tumor was not recognizable either clinically or by ultrasonography
(Figure 9B). The tumor has not recurred
during follow-up of 11 months.
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Figure 7. Case 3. A, Choroidal hemangioma
extending into the submacular region accompanied by a prominent serous detachment
of the sensory retina. B, Ultrasonographic study showing a solid choroidal
lesion with an accompanying retinal detachment on B-scan; high internal reflectivity
and a thickness of 3.9 mm was seen on A-scan ultrasonography.
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Figure 8. Case 3. Sketch showing outline
of the choroidal hemangioma, the extension of the exudative detachment through
the macula, and the relative locations of the overlapping laser applications
following the infusion of verteporfin.
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Figure 9. Case 3. A, The appearance of the
fundus 2 months following treatment showing the resolution of the sensory
retinal detachment. B, The posttreatment ultrasonographic study showed no
measurable tumor at the same relative site shown in Figure 7B.
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COMMENT
The management of circumscribed choroidal hemangiomas with secondary
retinal detachments has included photocoagulation, cryotherapy, radiation
from proton beam, episcleral plaque brachytherapy, and, more recently, TTT.
Laser photocoagulation may be successful in causing a regression of the exudative
detachment, but recurrence of the detachment often is evident within a year,
and the body of the tumor usually is not significantly affected. Brachytherapy
using radiolabeled iodine 125 or ruthenium 106 has been reported as being
effective by Madreperla et al.1 Brachytherapy
using radiolabeled cobalt 60 or 106Ru has also been reported as
being effective by Zografos et al2 in 1996
but, more recently, Zografos et al3 advocated
proton beam therapy. Successful treatment with proton beam was also reported
by Hannouche et al.4 While radiotherapy may
destroy the hemangiomas, late complications of radiotherapy, including radiation
maculopathy and optic neuropathy, may limit the therapeutic benefit.
Transpupillary thermotherapy has gained advocates of this modality as
a primary treatment for circumscribed hemangioma.5-8
Although successful tumor regression has been reported, the regressions have
often been incomplete with conventional TTT, and there is the real potential
TTT may produce nerve fiber bundle defects as well as preretinal fibrosis
in the macular region. Both of these complications have been observed in cases
with small choroidal melanomas that have been successfully treated with TTT.9 However, published reports of choroidal hemangioma
managed with TTT do not mention the complications of visual field defects
from nerve fiber bundle damage.
To minimize the potential for retinal damage with TTT, Kamal et al8 advocated enhancing the absorption of heat energy
in the choroid by using an infusion of indocyanine green 20 seconds prior
to treatment. The authors were able to deliver the energy with 1-minute applications
using powers up to 1250 mW. Half of the patients reported by Kamal et al8 received 2 treatments; the tumors regressed to a nonmeasurable
scar in 5 of 6 eyes. Visual fields were not reported.
The successful treatment of circumscribed choroidal hemangioma with
PDT, reported by Barbazetto and Schmidt-Erfurth,10
prompted the consideration of PDT as an attractive management option for treating
the choroidal hemangiomas in the present series. Because the success of PDT
depends not on a thermal effect but a photochemical effect, it was predicted
that PDT could successfully cause regression of the hemangiomas without causing
retinal damage and nerve fiber bundle field defects. This was a particularly
important consideration because, in each of the cases in this report, the
tumor abutted the optic nerve for approximately 120°, and nerve fiber
bundle damage could potentially cause a considerable loss of peripheral field.
The thickness of the choroidal hemangiomas in the present series ranged
from 2.4 to 3.9 mm, and exudative retinal detachments involved the macula
in each. Following PDT the serous detachment resolved in all eyes. The visual
acuity improved to 20/20 in the 2 eyes with extrafoveal hemangiomas, and the
tumors regressed to nonmeasurable thicknesses in all. Two patients were treated
with 2 sessions of PDT because of incomplete tumor regression observed at
a 6-week follow-up. Based on the complete regression of the tumor at 5 months
for patient 2, it seems reasonable to wait for up to 5 months before considering
the need for a second treatment.
After images induced by staring for 83 seconds at the retina illuminated
by the red aiming beam during treatment can confuse identification of the
boundaries of the choroidal hemangiomas that subtly blend in with the color
of normal choroid. Because of these disturbing after images, a preoperative
sketch outlining the tumor and the related retinal vessels has proven valuable
in helping define landmarks during treatment.
The successful short-term results with complete resolution of the choroidal
hemangioma in these cases and the absence of nerve fiber bundle defects after
PDT, as determined by Goldmann field perimetry, suggest that PDT may offer
significant advantages over other treatment modalities. Although long-term
complications are not expected after either PDT or TTT, the lack of consistent
complete tumor regression with TTT and the complete regression in 5 cases
of choroidal hemangioma (the 2 cases reported by Barbazetto and Schmidt-Erfurth10 and the 3 cases reported herein) suggest PDT is a
satisfactory primary treatment for circumscribed choroidal hemangioma when
treatment is indicated because of the presence of an exudative detachment
extending into the macula. Although it is possible that overlapping laser
exposures, as used in these cases, may increase the risk for damage to the
retina by overexposure, the Goldmann visual fields did not demonstrate a nerve
fiber bundle–type field defect as I have commonly observed after treating
choroidal melanomas with TTT. Whereas it may be possible to treat choroidal
hemangiomas without overlapping lesions, this treatment was given for the
choroidal hemangioma without any treatment precedent except the 2 case reports
published by Barbazetto and Schmidt-Erfurth.10
Subsequent to the submission of this manuscript, 3 additional cases of circumscribed
choroidal hemangiomas have been successfully treated with PDT.11
Details regarding administration of PDT were not given for those cases.
Presently PDT seems to be an attractive and an effective option for
treating circumscribed choroidal hemangiomas that are threatening central
vision or have caused visual loss from a secondary exudative retinal detachment.
Tumor recurrences have not been seen at follow-ups from 11 to 16 months. However,
longer follow-up will be important to observe for tumor recurrences.
AUTHOR INFORMATION
Submitted for publication October 30, 2001; final revision received
March 29, 2002; accepted April 12, 2002.
This study was supported in part by Research to Prevent Blindness Inc,
New York, NY, and by the Mayo Foundation, Rochester, Minn.
Reprints: Dennis M. Robertson, MD, Department of Ophthalmology, Mayo
Clinic, Rochester, MN 55905 (e-mail: robertson.dennis{at}mayo.edu).
From the Department of Ophthalmology, Mayo Clinic, Mayo Foundation,
and Mayo Medical School, Rochester, Minn.
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