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.

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