Clinical and Experimental Ophthalmology 2007; 35: 504505

doi: 10.1111/j.1442-9071.2007.01562.x

Editorial
Metastatic neoplasms to the intraocular structures
In this issue, Kanthan et al. have provided a comprehensive review
of metastatic cancer to the uvea with emphasis on evidencebased articles.1 They have used guidelines set forth by the Journal of
Clinical Oncology to provide levels of evidence and grades of
recommendation. The information obtained is derived from metaanalysis of well-designed controlled studies and well-designed
experimental studies. The authors have covered the subject of uveal
metastasis very well. As a full time ocular oncologist, I have, with
my associates, had extensive experience in the diagnosis and management of intraocular metastasis. Some of our experiences have
involved metastasis from unusual locations to various intraocular
structures. I would like to elaborate further on clinical features,
diagnostic approaches, and management.215

CLINICAL

FEATURES

The clinical features of an intraocular metastasis vary with the

location of the tumour. Iris metastasis may appear as one or more
yellow, white, or pink nodules in the iris stroma. It can be circumscribed or it can be friable and seed cells into the aqueous, producing a clinical picture of intraocular inflammation. A ciliary body
metastasis is often more difficult to detect clinically. It may appear
as a solitary mass or it can produce inflammatory signs, simulating
iridocyclitis. Secondary glaucoma frequently occurs, particularly
with iris and ciliary body tumours. Choroidal metastasis usually
appears as one or more yellow coloured lesions usually with
minimal or no signs of inflammation. It has a tendency to affect the
posterior choroid, frequently in the macular area. In contrast to iris
and ciliary body metastasis, choroidal metastasis tends not to
produce inflammatory signs, but usually causes a quiet secondary
serous retinal detachment. Although choroidal metastasis usually
has a yellow colour, metastasis from melanoma often has a grey or
brown colour and metastasis from carcinoid tumour, thyroid cancer
and renal cell carcinoma often has an orange colour. Retinal
metastasis, which is extremely rare, can simulate an occlusive retinal
vasculitis and can seed into the vitreous. Vitreous metastasis is also
rare and generally presents with tumour cells in the vitreous, resembling a primary inflammatory process or primary lymphoma. Optic
disc metastasis can develop by contiguous spread from juxtapapillary choroidal metastasis or it can involve only the optic nerve
where it produces a unilateral elevation of the optic disc. It must be
differentiated from papilloedema or optic papillitis.

DIAGNOSTIC

APPROACHES

The diagnosis of intraocular metastasis is generally made by taking

a history for prior cancers and by careful slit-lamp biomicroscopy
and ophthalmoscopy looking for the typical clinical features
described above. If a primary cancer has not been recognized, these
features should prompt a thorough system evaluation to detect the

primary malignancy. Ancillary studies such as fluorescein angiography, ultrasonography-computed tomography and magnetic resonance imaging can be of assistance in diagnosis.
Fluorescein angiography of a choroidal metastasis generally
shows beginning hyperfluorescence of the mass in the late venous
phase, usually later than with choroidal haemangioma or
melanoma. With ultrasonography it usually shows high internal
reflectivity with A-scan and acoustic solidity with B-scan, a pattern
similar to that seen with choroidal haemangioma. In the case of a
small iris or ciliary body metastasis, ultrasound biomicroscopy is a
recently used technique that can detect and determine the extent of
metastasis. In rare instances, a choroidal metastasis can assume a
mushroom configuration similar to choroidal melanoma.
In difficult cases that cannot be diagnosed with the aforementioned methods, transocular fine needle aspiration with cytologic
evaluation of aspirate can be used to establish the diagnosis. This
method can reliably identify the malignant cells and immunohistochemistry can be used to further localize the primary neoplasm
when necessary.13

PATHOLOGY
Most intraocular metastases are diagnosed clinically and no histopathologic material is available. However, uveal metastasis can
assume many gross and microscopic patterns.
Grossly, is usually white or yellow in colour and sessile, nodular,
or diffuse. Histopathology of uveal metastasis varies considerably,
depending on the type, primary site and degree of differentiation.
Some tumours are so poorly differentiated that the primary site is
difficult to determine based on examination of the ocular tissue. In
such instances immunohistochemistry may be of some value in
classifying the neoplasm and in determining the primary site.

MANAGEMENT
Management options for uveal metastasis vary with the clinical
situation and have been thoroughly covered in the accompanying
article by Kanthan et al.1 Small asymptomatic tumours or those that
have responded to prior or present chemotherapy may require no
immediate treatment and can be followed periodically. It is common
for a patient to be referred for irradiation and examination to disclose that the tumour is entirely inactive, having been cured locally
by prior systemic chemotherapy hormone therapy. The referring
oncologist is informed that the treatment is not necessary in such
cases. Larger symptomatic tumours may require external beam irradiation or plaque radiotherapy. The techniques of these methods
have been reported.14,15

PROGNOSIS
The systemic prognosis varies with the type of tumour. Patients
with choroidal metastasis from breast cancer often have a more

2007 The Author

Journal compilation 2007 Royal Australian and New Zealand College of Ophthalmologists

Editorial
favourable prognosis while those from lung cancer or melanoma
often have a worse prognosis. Patients with metastasis from carcinoid tumour often have a much better prognosis, and metastatic
foci from this tumour can remain relatively dormant for months or
years.
In summary, the diagnosis and management of uveal metastasis
can sometimes be complex and difficult. However, knowledge of
demographics, clinical features ancillary diagnostic studies and
options in management can be of assistance in making the best
decisions for patient care. The evidence-based analysis provided in
the accompanying study1 should provide the ophthalmologist,
general oncologists and radiation oncologists with sufficient information to effectively manage affected patients.

Jerry A Shields MD
Ocular Oncology Service, Wills eye Institute, Thomas Jefferson
University, Philadelphia, Pennsylvania, USA

REFERENCES
1. Kanthan GL, Jayamohan J, Yip D, Conway RM. Management
of metastatic carcinoma of the uveal tract: an evidence based
analysis. Clin Experiment Ophthalmol 2007; 35: 55365.
2. Shields JA, Shields CL. Metastatic tumors to the uvea, retina,
and optic disc. In: Shields JA, Shields CL, eds. Intraocular Tumors.
A Textbook and Atlas, 2nd edn. Philadelphia, PA: Lippincott,
Williams & Wilkins, 2007 (in press).
3. Shields JA, Shields CL. Metastatic tumors to the intraocular
structures. In: Shields JA, Shields CL, eds. Intraocular Tumors. A
Text and Atlas. Philadelphia, PA: WB Saunders, 1992; 20738.
4. Shields CL, Shields JA, Gross N, Schwartz G, Lally S. Survey of
520 uveal metastases. Ophthalmology 1997; 104: 126576.

505
5. Shields JA, Shields CL, Kiratli H, De Potter P. Metastatic
tumors to the iris in 40 patients. Am J Ophthalmol 1995; 119:
42230.
6. Shields JA, Shields CL, Singh AD. Metastatic neoplasms in the
optic disc in 30 cases: the 1999 Bjerrum Lecture: part 2. Arch
Ophthalmol 2000; 118: 21724.
7. Gunduz K, Shields JA, Shields CL, Eagle RC Jr, Ehya H,
McLaughlin W Jr. Lung carcinoma metastatic to the vitreous
cavity. Retina 1998; 18: 2856.
8. DePotter P, Shields CL, Shields JA, Tardio DJ. Uveal metastasis
from prostate carcinoma. Cancer 1993; 71: 27916.
9. Hykin PG, Shields JA, Shields CL, DePotter PV, Kehrli WH.
Carcinoid tumour metastatic to the choroid. Br J Ophthalmol
1996; 80: 84523.
10. Gunduz K, Shields JA, Shields CL, DePotter P, Wayner MJ.
Ewings sarcoma metastatic to the iris. Am J Ophthalmol 1997;
124: 5502.
11. Shields JA, Shields CL, Perez N. Choroidal metastasis from
medullary thyroid carcinoma in multiple endocrine neoplasia.
Am J Ophthalmol 2002; 134: 6079.
12. Shields JA, Carvalho C, Shields CL, Singh AD, Wagner D.
Bilateral choroidal metastasis from adenoid cystic carcinoma of
the submandibular gland. Retina 2000; 20: 4067.
13. Shields JA, Shields CL, Ehya H, Eagle RC Jr, DePotter P. Fine
needle aspiration biopsy of suspected intraocular tumors. The
1992 Urwick Lecture. Ophthalmology 1993; 100: 167784.
14. Shields CL, Shields JA, De Potter P et al. Plaque radiotherapy in
the management of uveal metastasis. Arch Ophthalmol 1997; 115:
2039.
15. Rudoler SB, Shields CL, Corn BW et al. Functional vision is
improved in the majority of patients treated with external beam
radiotherapy for choroidal metastasis: a multivariate analysis of
188 cases. J Clin Oncol 1997; 15: 124451.

2007 The Author

Journal compilation 2007 Royal Australian and New Zealand College of Ophthalmologists