Download Pars Plana Vitrectomy in Eyes Containing a Treated Posterior Uveal

Pars Plana Vitrectomy in Eyes Containing a
Treated Posterior Uveal Melanoma
WILLIAM J. FOSTER, MD, PHD, J. WILLIAM HARBOUR, MD, NANCY M. HOLEKAMP, MD,
GAURAV K. SHAH, MD, AND MATTHEW A. THOMAS, MD
● PURPOSE:
To determine the safety of pars plana vitrectomy in eyes containing a treated posterior uveal melanoma.
● DESIGN: Interventional case series.
● METHODS: Retrospective case series of patients with
posterior uveal melanoma who underwent pars plana
vitrectomy. Complications, vitreous cytology, local tumor control, and metastasis were assessed.
● RESULTS: Nine patients met study criteria. Tumors
were treated with 125I plaque radiotherapy (seven patients) or transpupillary thermotherapy (two patients).
Vitrectomy was performed for vitreous hemorrhage (five
patients), macular pucker (two patients), macular hole
(one patient), and rhegmatogenous retinal detachment
(one patient). Vitrectomy was performed at a mean of
24.7 months (range, 7– 47 months) after melanoma
treatment. Dispersion of tumor cells at vitrectomy was
not observed in any patients. Melanoma cells were
detected in the vitreous aspirate in one of seven cases
examined cytologically. This patient had intratumoral
and vitreous hemorrhage before plaque radiotherapy,
underwent combined vitrectomy/cataract extraction, and
developed intraocular tumor dissemination 56 months
after vitrectomy. No other patients developed intraocular
tumor dissemination. At mean follow-up of 24 months
(range, 3– 63 months) after vitrectomy, none of the nine
patients developed systemic metastasis.
● CONCLUSIONS: Pars plana vitrectomy rarely may lead
to intraocular tumor dissemination, although the risk of
this complication is probably low if the tumor has been
treated and has responded to therapy before vitrectomy.
Vitrectomy should be approached with caution if a
vitreous hemorrhage is present, especially if the hemorAccepted for publication Feb 24, 2003.
InternetAdvance publication at ajo.com June 18, 2003.
From the Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, and Barnes Retina Institute, St.
Louis, Missouri.
This study was presented in part at the combined meeting of the
Vitreous and Retina Societies, San Francisco, California, October 2002.
Inquiries to J. William Harbour, MD, Department of Ophthalmology
and Visual Sciences, Washington University School of Medicine, Campus Box 8096, 660 South Euclid Ave, St. Louis, MO 63110; fax: (314)
747-5073; e-mail: [email protected]
0002-9394/03/$30.00
doi:10.1016/S0002-9394(03)00244-7
©
2003 BY
rhage occurred before tumor treatment, as this may seed
tumor cells into the vitreous cavity. (Am J Ophthalmol
2003;136:471– 476. © 2003 by Elsevier Inc. All rights
reserved.)
P
OSTERIOR UVEAL MELANOMA OCCASIONALLY MAY
coexist in the same eye with a visually significant
retinal disorder that is treatable by pars plana vitrectomy, such as rhegmatogenous retinal detachment, macular hole, macular pucker, and vitreous hemorrhage.1
However, vitrectomy potentially may induce intraocular or
extraocular tumor dissemination, and it remains unclear
whether vitreous surgery is safe to perform in this setting.
Several studies have established the safety of cataract
surgery in eyes containing a melanoma treated with plaque
or charged particle radiotherapy.2– 4 However, cataract
surgery typically does not require entry into the posterior
segment or manipulation of the vitreous in proximity to
the melanoma. Repair of rhegmatogenous retinal detachments by scleral buckling techniques in melanoma-containing eyes appears to be safe, especially if external
drainage can be avoided.1,5 There are few reports of pars
plana vitrectomy in eyes containing uveal melanomas.
Radtke and coworkers6 described a single patient who
underwent vitrectomy for persistent exudative retinal detachment after plaque radiotherapy; this patient had no
evidence of tumor dissemination at 37 months after
surgery. Another case report described a patient who
underwent vitrectomy for excision of a presumed subfoveal
choroidal neovascular membrane that proved histopathologically to be a uveal melanoma. No tumor dissemination
was reported, but there was limited follow-up of only 7
months. A multicenter, retrospective study from five institutions reported the results of retinal reattachment surgery
in 10 patients with coexisting posterior uveal melanomas,1
but only two of these patients underwent pars plana
vitrectomy. Neither patient developed dissemination after
approximately 4 years of follow-up.
In this study, we provide further information on the
safety of pars plana vitrectomy in eyes containing a treated
posterior uveal melanoma by presenting the ocular and
systemic findings in nine patients from a single institution.
ELSEVIER INC. ALL
RIGHTS RESERVED.
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TABLE 1. Initial Patient Features and Pretreatment Tumor Characteristics
Patient
Age
Sex
Race
Eye
Basal Tumor
Dimensions (mm)
Tumor
Thickness (mm)
Tumor
Location
Tumor Treatment
1
2
3
4
5
6
7
8
9
64
52
61
54
57
68
73
71
84
M
M
M
M
M
F
M
M
M
W
W
W
W
W
W
W
W
W
Right
Left
Left
Right
Left
Left
Right
Right
Left
7⫻5
15 ⫻ 12
10 ⫻ 9
9⫻8
10 ⫻ 7
9⫻7
12 ⫻ 10
12 ⫻ 11
7⫻6
2.9
4.3
8.0
10.9
2.5
2.5
5.7
4.0
3.5
Posterior
Posterior
Posterior
Anterior
Posterior
Posterior
Anterior
Anterior
Anterior
Plaque
Plaque ⫹ TTT
Plaque
Plaque
TTT
TTT
Plaque
Plaque
Plaque
F ⫽ female; M ⫽ male; TTT ⫽ transpupillary thermotherapy; W ⫽ white.
dimensions, and thickness at vitrectomy. Results of cytologic examination of vitreous specimen were recorded in
the seven cases in which this was performed (in the other
two cases the surgeon elected not to obtain cytologic
analysis). Follow-up data recorded included date of last
follow-up and ocular and systemic status at last follow-up.
Results of histopathologic evaluation of enucleated globes
were recorded when available.
METHODS
THIS STUDY WAS PERFORMED WITH APPROVAL OF THE
Institutional Review Board of Washington University.
Patients were identified by computer search of the Barnes
Retina Institute medical records for patients with a diagnosis of uveal melanoma who underwent pars plana vitrectomy. Patients were included if they underwent
treatment for a posterior segment tumor that was typical
for uveal melanoma based on clinical and ultrasonographic
examination7 and if they underwent a three-port pars
plana vitrectomy for a vitreoretinal disorder. Patients were
excluded if the vitrectomy was performed in conjunction
with local surgical resection of an iridociliary melanoma.
Nine patients who underwent vitrectomy between October 1990 and May 2002 met these criteria. Patient 4 was
previously reported1 but subsequently developed further
findings that are described herein.
Plaque radiotherapy was performed with standard Collaborative Ocular Melanoma Study (COMS) style plaques
and 125I radioactive seeds calculated to deliver 85 to 90 Gy
to the tumor apex over 4 days. Transpupillary thermotherapy was performed in three treatment sessions, with subsequent tumor flattening, as previously described.8 Each
patient underwent a standard three-port vitrectomy. In
most cases, the vitrectomy cassette containing the vitreous
aspirate was sent for cytologic examination, which was
performed by spinning down the aspirate, smearing it onto
slides, and staining with Papanicolou or DiffQuick stain.
Baseline data recorded for each patient included patient
age, sex, race, involved eye, tumor basal dimensions
(estimated by indirect ophthalmoscopy), and thickness
(estimated by A-scan ultrasonography) at diagnosis, tumor
location (posterior vs anterior to the equator), tumor
treatment, and date. Data related to the vitrectomy that
were recorded included date of surgery, indication for
vitrectomy, surgical procedures performed, tumor basal
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RESULTS
NINE PATIENTS MET INCLUSION CRITERIA FOR THE STUDY.
Patient data and initial tumor characteristics are summarized in Table 1. In all nine patients, the tumor was treated
before vitrectomy. 125I plaque radiotherapy was used as the
only treatment in six patients, transpupillary thermotherapy (TTT) alone was used in two patients, and 125I plaque
radiotherapy combined with TTT was used in one patient.
The mean largest basal tumor dimension before tumor
treatment was 10.1 mm (median, 10 mm; range, 7–15
mm), and the mean tumor thickness was 5.0 mm (median,
9 mm; range, 2.5 –10.9 mm). The tumor location was
juxtapapillary in three cases, anterior to the equator in
three cases, between the temporal vascular arcades and the
equator in two cases, and macular in one case.
All patients underwent a three-port pars plana vitrectomy (Table 2). The mean time from initial tumor treatment (either plaque implantation or initial TTT) to
vitrectomy was 24.7 months (median, 27; range, 7– 47
months). The indications for vitrectomy included vitreous
hemorrhage (five patients), macular pucker (two patients),
macular hole (one patient), and rhegmatogenous retinal
detachment (one patient). Vitreous hemorrhage occurred
before tumor treatment in one case (Patient 4) and after
tumor treatment in four patients. Tumor treatment caused
a decrease in tumor thickness before vitrectomy in all
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TABLE 2. Summary of Pars Plana Vitrectomy Data
Patient
Reason for
Vitrectomy
Interval From Tumor
Treatment to
Vitrectomy (months)
Tumor Thickness at
Vitrectomy (mm)
Additional
Procedures at
Vitrectomy
Melanoma Cells
by Vitreous
Cytology
Follow-up After
Vitrectomy (months)
Intraocular Tumor
Dissemination at Final
Follow-up
Metastasis
at Final
Follow-up
1
2
3
4
5
6
7
8
9
VH
VH
VH
VH
Pucker
Pucker
RhRD
VH
MH
47
30
32
19
22
27
7
29
13
2.0
0
3.8
2.4
1.4
0
3.0
0
2.2
MP,EL
EL
EL
CE
MP
MP
FAE,EL
CE
MP, FAE
ND
Negative
Negative
Positive
Negative
Negative
Inconclusive
ND
Negative
5
17
2
56
12
5
63
53
3
No
No
No
Yes
No
No
No
No
No
No
No
No
No
No
No
No
No
No
CE ⫽ cataract extraction and implantation of posterior chamber lens; EL ⫽ endolaser photocoagulation; FAE ⫽ fluid–air exchange; MH ⫽
macular hole; MP ⫽ membrane peeling; ND ⫽ not done; RhRD ⫽ rhegmatogenous retinal detachment; VH ⫽ vitreous hemorrhage.
cases. The mean tumor thickness at the time of vitrectomy
was 1.6 mm (median, 1.37 mm; range, 0 –3.8 mm). In no
case was there evidence at the time of vitrectomy that the
surgical procedure disrupted the tumor or dispersed tumor
cells. Additional surgical procedures during vitrectomy
included endolaser photocoagulation (four patients),
membrane peeling (four patients), fluid–air exchange (two
patients), cataract extraction (two patients), and internal
drainage of subretinal fluid (one patient).
The vitreous aspirate was sent for cytologic examination
in seven patients. Scant cells were found in the vitreous
aspirates and were interpreted as negative for malignant
cells in five patients, suspicious for malignant cells in one
patient (Patient 7), and positive for malignant cells in one
patient (Patient 4) based on cytomorphologic features (for
example, prominent nucleolus, nuclear atypia). After
mean follow-up of 24 months (range, 3– 63 months), eight
of the nine patients showed no evidence of intra- or
extraocular tumor dissemination. Patient 4 developed
intraocular tumor dissemination and is described in detail
below. None of the nine patients developed metastatic
disease.
CASE REPORT
A 54-YEAR-OLD MAN PRESENTED WITH FLOATERS AND
blurred vision in the right eye. His visual acuity in that eye
was 20/25, and he was found to have a rhegmatogenous
retinal detachment in the nasal periphery associated with
three retinal breaks. In the superonasal quadrant of the
same eye, an elevated mushroom-shaped, brown tumor was
present. The tumor basal dimensions were 9 ⫻ 8 mm, and
the ultrasound thickness was 10.9 mm. The internal
reflectivity was consistent with a uveal melanoma. The
VOL. 136, NO. 3
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retinal detachment was repaired by pneumatic retinopexy
with 0.3 ml perfluorethane (C2F6) gas and indirect laser
photocoagulation to the retinal breaks, which was followed
by prompt retinal reattachment. However, 1 week later the
patient complained of sudden vision loss and was found to
have a moderate vitreous hemorrhage. Blood appeared to
be emanating from the tumor surface. Three months were
allowed for the vitreous hemorrhage to clear, and the
patient was then treated with 125I plaque radiotherapy.
The tumor subsequently responded with marked shrinkage.
Nevertheless, recurrent vitreous hemorrhages persisted.
Two years later, the tumor had regressed to a thickness of
2.4 mm, but visual acuity had dropped to 20/200 owing to
persistent vitreous hemorrhage and cataract. The patient
underwent pars plana vitrectomy combined with phacoemulsification and posterior capsulotomy. The vitreous
aspirate was sent to cytology and was found to contain
definite melanoma cells. The postoperative visual acuity
improved to 20/50. The tumor continued to regress with
no evidence of local recurrence. Neovascular glaucoma
was treated with panretinal photocoagulation. The vision
eventually declined to light perception owing to radiation
retinopathy. Two years later (76 months after initial
presentation and 54 months after vitrectomy), the right
eye became painful and was noted to have elevated
intraocular pressure and multiple, lightly pigmented nodules in the anterior chamber angle and iris stroma, consistent with intraocular tumor dissemination (Figure 1). The
eye was enucleated, and histopathologic examination revealed diffuse seeding of melanoma cells along the vitreous
base and on the posterior and anterior iris surfaces, with
multiple tumor nodules invading the anterior chamber
angle and iris stroma. Only a flat scar of the primary tumor
remained. Eight months later, the patient remained free of
metastatic disease.
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FIGURE 1. Intraocular dissemination of posterior uveal melanoma 54 months after combined pars plana vitrectomy, cataract
extraction, and posterior capsulotomy (Patient 4). (A) Slit-lamp photograph of right eye, showing light brown tumor nodules in the
anterior chamber angle at 6:00 and 9:00 o’clock. (B) Goniophotograph showing same tumor nodules reversed in mirror (white
arrows). Note prominent iris vessels feeding the tumor nodules (black arrow). (C) Digitally enhanced composite photomicrograph
showing tumor nodule invading the anterior chamber angle and a smaller tumor nodule on the iris stroma near the pupil. (D, E) Melanoma
cells in the vitreous base overlying the pars plana and migrating anteriorly along the ciliary processes (arrow). (F) The primary uveal
melanoma, treated with plaque radiotherapy 19 months before vitrectomy, demonstrating complete regression to a flat scar. Note residual
pigment-laden macrophages and overlying atrophic retina (hematoxylin-eosin staining, original magnification ⴛ40).
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DISCUSSION
IN THIS ARTICLE, WE PRESENT NINE PATIENTS WHO UNDER-
went pars plana vitrectomy for repair of a vitreoretinal
abnormality after treatment of a posterior uveal melanoma
in the same eye. This represents the largest series reported
to date. Seven tumors were treated with plaque radiotherapy and two with transpupillary thermotherapy. In all
cases, the tumor regressed substantially before vitrectomy.
In six of seven patients in whom the vitreous aspirate was
examined for cytology, malignant cells were not found, and
in eight of the nine patients, no intraocular or extraocular
tumor dissemination occurred. In one patient, intratumoral bleeding and vitreous hemorrhage occurred before
plaque radiotherapy, melanoma cells were found in the
vitreous aspirate, and diffuse intraocular tumor dissemination occurred subsequent to combined cataract extraction/
vitrectomy. We conclude that pars plana vitrectomy in an
eye containing a previously treated uveal melanoma is
probably safe in most patients, as long as the tumor has
responded to treatment before vitrectomy and there was no
vitreous hemorrhage before tumor treatment to indicate
possible retinal perforation and tumor dispersion.
Patient 4 developed intraocular tumor dissemination 54
months after vitrectomy. Several factors may have contributed to the poor outcome in this case. First, vitreous
hemorrhage from intratumoral bleeding occurred before
treatment of the tumor and may have allowed viable tumor
cells to disseminate into the vitreous. Vitreous hemorrhage
is encountered not infrequently with in eyes containing a
posterior uveal melanoma, but intraocular tumor dissemination in such patients (most of whom have not undergone subsequent vitrectomy) is extremely rare, suggesting
that the vitrectomy in this patient may have contributed
to the tumor dissemination. A similar case was reported by
Laqua and associates9 in which vitrectomy was performed
for vitreous hemorrhage in an eye that was found intraoperatively to contain a melanoma. Intraocular tumor dissemination subsequently developed, with histopathologic
findings similar to our patient. In contrast, tumor dissemination occurred in none of the four patients who developed a vitreous hemorrhage after tumor treatment. The
nonclearing vitreous hemorrhage in this case also prevented adequate clinical examination of the posterior
segment, which may have revealed the disseminated tumor. In addition, cataract extraction and posterior capsulotomy at the time of vitrectomy potentially may have
provided access for tumor cells into the anterior chamber.
Shortcomings of this study include the small number of
patients and limited follow-up. Thus, firm conclusions
cannot be drawn from this study. However, this is the
largest series reported so far, and provisional guidelines
from this study may be useful until a larger study is
conducted. First, treatment of the melanoma, preferably
with irradiation, should be probably be performed before
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VITRECTOMY
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ble. Several reports have documented intraocular tumor
recurrence in patients who underwent vitrectomy without
tumor irradiation.9 –11 The lack of tumor dissemination in
eight of our nine patients (89%), all of whom underwent
tumor treatment before vitrectomy, suggests that tumor
dissemination may be less likely if the tumor has been
previously treated. Plaque radiotherapy destroys the reproductive integrity of melanoma cells by inducing DNA
damage.12 Therefore, any melanoma cells that might
disseminate into the vitreous during vitrectomy would be
expected to be nonviable. It is not clear how long one
should wait to perform vitrectomy after tumor treatment.
The shortest time interval in our series was 7 months, and
no tumor dissemination developed in this patient. Although this study does not allow us to conclude the
shortest safe interval between tumor treatment and vitrectomy, a definite treatment response (for example, resolution of exudative retinal detachment, decreasing tumor
thickness, change in tumor color) should probably be
observed before vitrectomy. Second, the vitreous aspirate
should be sent for cytologic examination at the time of
vitrectomy. The presence of malignant cells in the vitreous
should alert the physician to follow the patient carefully
for the possibility of tumor dissemination and possibly to
refrain from further intraocular surgery. Third, vitrectomy should be approached with caution in the presence
of a vitreous hemorrhage, particularly if the hemorrhage
occurred before tumor treatment. Vitreous hemorrhage
can be due to intratumoral bleeding, which may seed
tumor cells into the vitreous cavity, especially if the
tumor has broken through the Bruch membrane and
ruptured the overlying retina. Conservatively, one
should consider the possibility that any vitreous hemorrhage associated with a melanoma could potentially
contain malignant cells, even if other explanations are
possible.
In conclusion, we found no evidence of intraocular
tumor dissemination as a result of pars plana vitrectomy in
eight treated posterior uveal melanomas that were not
associated with vitreous hemorrhage before tumor treatment. Larger studies with longer follow-up will be needed
to determine the safety of vitrectomy in this setting.
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