Tumors to the Eye and Adnexa

Carol L. Shields



• Intraocular metastasis – most common tumor of the eye

• Most common site of involvement is choroid (63%)

• Other sites – iris, ciliary body (6%), vitreous, retina, optic disc, eyelid, and orbit (32%)

• 25% of patients have no known history of cancer. Primary site remains unknown in 10%

• Most common primary site – breasts in women and lungs in men



• Increasing incidence paralleling improving cancer survival rates

• True incidence unknown in view of poor detection because of advanced cancer stage and asymptomatic nature of disease

• Postmortem incidence 10%

• Estimated prevalence of uveal metastasis – 2.3–9.2% of all patients with systemic cancer

• Estimated prevalence of orbital metastasis – 2–4.7% of all patients with systemic cancer


• Risk factor for uveal metastasis – presence of metastatic disease in 2 or more organs

• 70–90% of patients have metastatic lesion elsewhere at time of ocular diagnosis

• Median time from diagnosis of primary cancer to ocular metastasis – 12–55 months, depending on the primary cancer site


Choroid has a rich vascular supply and is recognized as the tissue with the highest metastatic efficiency index (measure of metastatic deposits in relation to blood flow).


• Primary cancer sites that promote ocular metastasis (pooled from multiple studies)

– Breast cancer– 40–47%

– Lung cancer– 14–30%

– GI cancer– 4%

– Prostate cancer– 1–4%

– Melanoma – 5%

– Kidney cancer– 2–4%



• Most cases are asymptomatic

• Blurred vision is the most common presentation

• Other features

Uveal metastasis – pain, scotoma, redness, and photophobia

Orbital metastasis – diplopia, proptosis, pain, ptosis, and visible mass


Choroidal metastasis

– Bilaterality in 20–50%

– Multifocal lesions 30%

– Commonly affects posterior choroid, especially macula

– Usually cream colored lesions

– Orange color in metastasis from bronchial carcinoid, renal cell carcinoma, and thyroid cancer.

– Gray–brown color in melanoma metastasis

– Extensive subretinal fluid in active lesions

– “Leopard skin appearance” – due to clumps of brown pigment

Iris metastasis

– Yellow to white single or multiple nodules

– Other likely features – iridocyclitis, hyphema, and glaucoma

Ciliary body metastasis

– Solitary sessile or dome shaped

– Other features – cataract, iridocyclitis, and hyphema

Retinal metastasis

– Resemble occlusive vasculitis

– Vitreous seeding may be present

Vitreous metastasis

– Tumor infiltration of vitreous resembling lymphoma

Optic nerve metastasis

– Occurs as juxtapapillary spread from choroidal metastasis or isolated optic nerve involvement

– Unilateral optic nerve elevation

– Significant visual loss observed

Orbit metastasis

– Mass effect causing proptosis, globe displacement, pain, chemosis, and eyelid swelling

– Soft tissue infiltration – ptosis, restricted extraocular movement

– Enophthalmos in scirrhous carcinoma (commonly breast and stomach metastasis)

– Carcinoid – frequently, orbital metastasis is the first sign.

– Primary small intestinal carcinoids typically metastasizes to orbit and bronchial carcinoid metastasizes to choroid

– Pediatric population – metastasis are rare but the most likely primary sites are– neuroblastoma, Wilms tumor, Ewing’s sarcoma, rhabdomyosarcoma

Eyelid metastasis

– Varied presentation – solitary or multiple nodules or diffuse lid infiltration


Initial approach

• Diagnosis primarily clinical

• CNS imaging of paramount importance because of coexistent brain metastasis


Uveal metastasis

– Fluorescein angiography – early hypofluorescence and late leakage

– Ultrasound –

A-scan – moderate to high internal reflectivity

B-scan – Acoustic solidity

Rarely mushroom shaped configuration noted

Ultrasound biomicroscopy useful for ciliary body metastasis

Orbital metastasis

– CT and MRI primary diagnostic tests – MRI provides better soft tissue resolution. CT appropriate for imaging bony lesions (e.g., Prostatic metastasis)

Diagnostic Procedures/Other

• Definitive diagnosis – fine needle aspiration biopsy or open biopsy

• Immunohistochemistry beneficial in select cases to diagnose primary cell type

Pathological Findings

• Orbital tissue metastasis rate – bone–fat-muscle ratio – 2:2:1

• Diagnosis of ocular metastasis consistent with Stage IV cancer

• Work up with oncologist required for restaging tumor and investigating for other sites of metastasis


Choroidal metastasis

– Melanoma/nevus

– Hemangioma

– Osteoma

– Lymphoma

– Inflammatory diseases

Iris metastasis

– Amelanotic melanoma/nevus

– Granulomas

Orbit/Eyelid metastasis

– Benign and malignant orbital/eyelid tumors


Uveal Metastasis

External beam radiotherapy (Grade B treatment recommendation)

– Dose – 20–50 Gy

– Response – 63–83%

– Visual improvement – 27–89%

– Complications – ocular surface changes, cataract, and radiation retinopathy

Systemic chemotherapy/Hormonal therapy

– Success based on type of primary tumor

– Useful in breast/lung cancer

Plaque radiotherapy

– High dose targeted radiation dosage

– Useful for solitary choroidal metastasis

– Beneficial for recurrent tumor following external beam radiation

Proton beam therapy

– Shorter duration of therapy

– More precise tissue targeting due to minimal scatter

Local therapy

– Transpupillary thermotherapy, laser photocoagulation, photodynamic therapy

– Can be used as adjuvant treatment to radiation

– Isolated reports of successful treatment with intravitreal bevacizumab – role unknown


– Indicated for blind painful eye due to glaucomatous damage

Orbit Metastasis

• Treatment considerations dependent on systemic features and life expectancy.

• External beam radiotherapy – primary treatment modality

– Advantages – decrease tumor size, reduce proptosis, preserve vision

– Dose – 20–40 Gy over 2–4 weeks

– Complications – Cataract, Radiation retinopathy

– Concurrent intracranial irradiation required for brain metastases

• Systemic chemotherapy – reserved for chemosensitive tumors like small cell lung cancer

• Hormonal therapy – Breast/prostate metastasis

• Orbital surgery – debulking reserved to reduce ocular pain, proptosis, and diplopia

• Exenteration – for disfiguring orbital mass

EyelID Metastasis

• Dependent on tumor size, location, extent, and systemic features.

• Excisional biopsy – Small solitary lesion

• External beam radiotherapy – for multiple/recurrent lesions

• Systemic chemotherapy/immunotherapy – for extensive systemic metastasis

• Palliative care – for terminal metastasis

• Topical Imiquimod – for cutaneous melanoma metastasis


General Measures

Treatment of primary tumor and other metastatic foci

Additional Therapies

• Palliative care

• Pain management


• In 3–5% of patients the primary site remains unknown after workup

• Following evaluation of all sites of metastasis, therapeutic chemotherapy trial can be attempted

• 85% of these patients die within 1 year



• Multidisciplinary coordinated care required

• Close monitoring for detection of systemic metastatic foci

• Close ophthalmic follow-up for detection of new metastasis, especially in the fellow eye


• Counsel regarding warning eye signs in patients with advanced cancers

• After diagnosis of ocular metastasis – careful monitoring is required to detect new metastasis in both eyes


• Median life expectancy – 6–9 months

• Prognosis dependent on type of tumor and extent of metastasis

• Favorable prognosis – Breast cancer and carcinoid metastasis


• Ahmad SM, Esmaeli B. Metastatic tumors of the orbit and ocular adnexa. Curr Opin Ophthalmol 2007;18:405–413.

• Bianciotto C, Demirci H, Shields CL, et al. Metastatic tumors to the eyelid: Report of 20 cases and review of the literature. Arch Ophthalmol 2009;127:999–1005.

• Kanthan GL, Jayamohan J, Yip D, et al. Management of metastatic carcinoma of the uveal tract: An evidence-based analysis. Clin Experiment Ophthalmol 2007;35:553–565.

• Shields JA, Shields CL, Kiratli H, et al. Metastatic tumors to the iris in 40 patients. Am J Ophthalmol 1995;119:422–430.

• Shields CL, Shields JA, Gross NE, et al. Survey of 520 eyes with uveal metastases. Ophthalmology 1997;104:1265–1276.

• Shields JA, Shields CL. Metastatic tumors to the uvea, retina, and optic disc. In: Shields JA, Shields CL, eds. Eyelid, Conjunctival, and Orbital Tumors. A Textbook and Atlas, 2nd ed. Philadelphia, PA: Lippincott, Williams & Wilkins, 2007;727–745, 168–173.

• 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 ed. Philadelphia, PA: Lippincott, Williams & Wilkins, 2007;198–227.

• Shields CL, Shields JA. Metastatic cancer to the eye and adnexa. In Tasman WS, Jaeger E, eds, Duane’s Clinical Ophthalmology Vol. 5, Chapter 34, Philadelphia, PA: Lippincott Williams & Wilkins, 2010.

See Also (Topic, Algorithm, Electronic Media Element)









198.4 Secondary malignant neoplasm of other parts of nervous system

198.2 Secondary malignant neoplasm of skin


• Increasing incidence of ocular metastasis

• High index of suspicion required for diagnosis

• Early diagnosis and appropriate therapy improves prognosis and visual morbidity.

• Ocular metastasis is the first presentation of malignancy in around 30%.

• Choroid is the most common site of metastasis.

• External beam radiotherapy is the treatment of choice in most patients.

Only gold members can continue reading. Log In or Register to continue

Stay updated, free articles. Join our Telegram channel

Nov 9, 2016 | Posted by in OPHTHALMOLOGY | Comments Off on Tumors to the Eye and Adnexa

Full access? Get Clinical Tree

Get Clinical Tree app for offline access