Ophthalmology — Metastatic Tumors to the Eye and Adnexa

Basics

Description

Intraocular metastasis is the most common malignant tumor involving the eye.

The choroid is the most common site, accounting for approximately 63% of ocular metastases because of its exceptionally rich vascular supply.

Other sites include:

• Orbit/adnexa: ~32%
• Iris and ciliary body: ~6%
• Retina
• Vitreous
• Optic disc/optic nerve
• Eyelid

An important diagnostic point is that ~25% of patients have no known malignancy when the ocular metastasis is discovered. Even after systemic investigation, the primary site remains unknown in approximately 10%.

Most common primary:

• Women → breast carcinoma
• Men → lung carcinoma

Epidemiology

The incidence of ocular metastasis is increasing, probably because patients with systemic malignancies are surviving longer.

The true incidence is difficult to determine because:

• Many lesions are asymptomatic.
• Patients may have advanced systemic disease.
• Small ocular metastases may remain undetected.

Reported figures include:

• Postmortem incidence: ~10%
• Uveal metastasis in systemic cancer: 2.3–9.2%
• Orbital metastasis in systemic cancer: 2–4.7%

Risk Factors

The major risk factor for uveal metastasis is widespread metastatic disease.

Approximately 70–90% of patients already have metastases elsewhere when ocular metastasis is diagnosed.

A particularly important risk factor is metastatic involvement of ≥2 other organs.

Median interval between diagnosis of the primary malignancy and ocular metastasis is approximately 12–55 months, depending on tumor type.

Pathophysiology

Ocular metastases usually spread hematogenously.

The choroid has one of the highest blood flows of any tissue in the body and therefore has an extremely high metastatic efficiency.

This explains why the choroid is much more commonly affected than the retina or other intraocular structures.

Common Primary Cancers

Approximate distribution:

Primary tumor

Approximate frequency

Breast

40–47%

Lung

14–30%

Melanoma

~5%

GI malignancy

~4%

Kidney

2–4%

Prostate

1–4%

Diagnosis

History

Many patients are asymptomatic.

When symptoms occur, the most common is:

Blurred vision

Uveal metastasis

Other symptoms include:

• Scotoma
• Pain
• Redness
• Photophobia

Orbital metastasis

Typical symptoms include:

• Diplopia
• Proptosis
• Pain
• Ptosis
• Visible or palpable mass

Choroidal Metastasis

The choroid is the classic and most common site of ocular metastasis.

Clinical Features

• Bilateral in 20–50%
• Multifocal in approximately 30%
• Usually located in the posterior choroid
• Frequently involves the macular region
• Typically cream-yellow or cream-colored
• Often associated with substantial subretinal fluid

Color Can Suggest the Primary

Orange choroidal metastasis may occur with:

• Renal cell carcinoma
• Thyroid carcinoma
• Bronchial carcinoid

Gray-brown metastasis may suggest:

• Metastatic melanoma

A “leopard-skin” appearance can occur from clumps of brown pigment.

Iris Metastasis

Typical appearance:

• Yellow-white nodule
• Single or multiple lesions

Associated findings may include:

• Anterior uveitis / iridocyclitis
• Hyphema
• Secondary glaucoma

Therefore, an unexplained unilateral anterior uveitis with an iris mass—particularly in a patient with malignancy—should raise suspicion for metastasis.

Ciliary Body Metastasis

Usually appears as a:

• Solitary
• Sessile or dome-shaped mass

Associated manifestations include:

• Cataract
• Iridocyclitis
• Hyphema

Ultrasound biomicroscopy (UBM) is particularly useful for evaluating these lesions.

Retinal Metastasis

Retinal metastases are uncommon.

They can resemble:

• Occlusive retinal vasculitis
• Retinal infiltrative disease

Vitreous tumor seeding may accompany retinal involvement.

Vitreous Metastasis

Tumor cells can infiltrate the vitreous and produce an appearance resembling:

Primary vitreoretinal lymphoma.

Optic Nerve Metastasis

May result from:

1. Juxtapapillary extension of a choroidal metastasis, or
2. Direct isolated optic nerve metastasis

Typical findings include:

• Unilateral optic disc elevation
• Significant visual loss

Orbital Metastasis

Orbital metastasis may produce a mass effect causing:

• Proptosis
• Globe displacement
• Pain
• Chemosis
• Eyelid swelling

Soft-tissue infiltration can cause:

• Ptosis
• Restricted extraocular movements
• Diplopia

Important Pearl — Enophthalmos

Unlike most orbital tumors, scirrhous metastatic carcinoma can cause enophthalmos rather than proptosis.

Classically associated with:

• Breast carcinoma
• Gastric carcinoma

Carcinoid Metastasis

Orbital metastasis can occasionally be the first manifestation of a carcinoid tumor.

A useful pattern:

• Small-intestinal carcinoid → orbit
• Bronchial carcinoid → choroid

Pediatric Orbital Metastases

Metastatic orbital tumors are uncommon in children.

Important primary tumors include:

• Neuroblastoma
• Wilms tumor
• Ewing sarcoma
• Rhabdomyosarcoma

Eyelid Metastasis

Presentation is variable and may include:

• Solitary nodule
• Multiple nodules
• Diffuse eyelid infiltration

Diagnostic Testing

Initial Approach

Diagnosis is often primarily clinical, especially in a patient with a known systemic malignancy and characteristic choroidal lesions.

However, brain/CNS imaging is important because ocular metastases may coexist with intracranial metastases.

Fluorescein Angiography

Choroidal metastases typically demonstrate:

• Early hypofluorescence
• Late hyperfluorescence/leakage

Ultrasonography

A-scan

Usually demonstrates:

Moderate-to-high internal reflectivity

This can help distinguish metastasis from melanoma, which generally has lower internal reflectivity.

B-scan

Typically demonstrates:

• Acoustic solidity
• Choroidal mass
• Associated subretinal fluid

A mushroom configuration is unusual but can occasionally occur.

Orbital Imaging

MRI

Preferred when detailed evaluation of:

• Orbital soft tissue
• Optic nerve
• Intracranial structures

is required.

CT

Especially useful for:

• Bone involvement
• Osteoblastic or destructive lesions

For example, prostate metastases may have prominent osseous involvement.

Biopsy

Definitive diagnosis can be obtained with:

• Fine-needle aspiration biopsy (FNAB)
• Open biopsy

Biopsy is particularly useful when:

• There is no known primary cancer.
• The lesion is atypical.
• The diagnosis will change systemic management.

Immunohistochemistry can help identify the tissue of origin.

Important Systemic Implication

Detection of ocular metastasis generally indicates:

Stage IV systemic malignancy.

The patient therefore requires oncologic evaluation for:

• Restaging
• Identification of additional metastatic sites
• Selection of systemic treatment

Differential Diagnosis

Choroidal Metastasis

Important mimickers include:

• Choroidal melanoma
• Choroidal nevus
• Choroidal hemangioma
• Choroidal osteoma
• Choroidal lymphoma
• Inflammatory choroidal lesions

Iris Metastasis

Consider:

• Amelanotic iris melanoma
• Iris nevus
• Inflammatory granuloma

Orbital/Eyelid Metastasis

Differential includes numerous:

• Benign orbital tumors
• Primary malignant orbital tumors
• Lymphoproliferative lesions
• Inflammatory orbital disease

Treatment

Treatment depends heavily on:

• Primary malignancy
• Extent of systemic disease
• Number and location of ocular lesions
• Visual potential
• Symptoms
• Expected survival

The overall goals are usually vision preservation and symptom control while treating systemic disease.

Uveal Metastasis

External Beam Radiotherapy

A traditional and effective treatment.

Typical dose:

20–50 Gy

Reported tumor response:

63–83%

Visual improvement:

27–89%

Possible complications include:

• Ocular surface disease
• Cataract
• Radiation retinopathy

Systemic Therapy

Systemic treatment may cause regression of ocular metastases.

Options depend on tumor biology and include:

• Chemotherapy
• Hormonal therapy
• Targeted therapy
• Immunotherapy

Systemic therapy is particularly important when widespread metastatic disease is present.

Plaque Radiotherapy

Useful particularly for:

• Solitary choroidal metastasis
• Localized disease requiring concentrated radiation
• Recurrence after external beam radiotherapy

It delivers a high radiation dose directly to the lesion while reducing exposure to surrounding tissues.

Proton Beam Therapy

Advantages include:

• Highly precise radiation delivery
• Reduced radiation scatter
• Potentially shorter treatment course

Other Local Treatments

Selected lesions may be treated with:

• Photodynamic therapy
• Transpupillary thermotherapy
• Laser photocoagulation

These are generally reserved for carefully selected localized tumors.

Enucleation

Rarely required.

Main indication:

Blind, painful eye, particularly from severe secondary glaucoma or extensive tumor involvement.

Orbital Metastasis

Treatment depends strongly on systemic prognosis.

External beam radiotherapy

Often the principal local treatment.

Typical dose:

20–40 Gy over approximately 2–4 weeks

Potential benefits:

• Tumor shrinkage
• Reduced proptosis
• Relief of pain
• Improved motility
• Preservation of vision

Complications include:

• Cataract
• Radiation retinopathy

Brain metastases may require concurrent intracranial radiation.

Systemic Therapy for Orbital Disease

Chemotherapy may be useful for chemosensitive tumors, particularly:

Small-cell lung carcinoma

Hormonal therapy can be useful for:

• Breast carcinoma
• Prostate carcinoma

Orbital Surgery

Surgical debulking is usually palliative rather than curative.

It may be performed to improve:

• Pain
• Severe proptosis
• Diplopia

Orbital exenteration is rarely indicated but may be considered for a severely disfiguring orbital tumor.

Eyelid Metastasis

Treatment depends on lesion number, size, location, systemic disease and prognosis.

Options include:

• Excisional biopsy for small solitary lesions
• External beam radiotherapy for multiple/recurrent lesions
• Systemic anticancer therapy for disseminated disease
• Palliative therapy in terminal disease

Unknown Primary Tumor

In a small proportion of patients, the primary tumor remains unknown despite systemic investigation.

These patients generally have a poor prognosis.

A systemic therapeutic trial may sometimes be considered after appropriate oncologic evaluation.

Follow-Up

Management requires coordinated multidisciplinary care involving:

• Ophthalmology/ocular oncology
• Medical oncology
• Radiation oncology
• Other specialists depending on the primary malignancy

Ophthalmic follow-up should monitor:

• Response of existing lesions
• Development of additional metastases
• Fellow-eye involvement
• Subretinal fluid
• Visual function
• Treatment-related complications

Prognosis

Historically, ocular metastasis indicates advanced systemic disease.

Reported median survival after diagnosis has been approximately:

6–9 months

However, prognosis varies considerably according to the primary malignancy, molecular subtype, treatment response, and extent of systemic disease.

Relatively more favorable survival is seen with:

• Breast carcinoma
• Carcinoid tumors

Key Clinical Pearls

• Choroid is the most common site of ocular metastasis.
• Breast cancer is the most common primary in women; lung cancer in men.
• Approximately 25% may have no known cancer when the ocular lesion is discovered.
• Choroidal metastases are classically cream-colored, posterior, and associated with subretinal fluid.
• They can be bilateral and multifocal, an important clue against primary choroidal melanoma.
• Orange metastasis → think renal cell, thyroid, or carcinoid.
• Gray-brown metastasis → consider metastatic melanoma.
• Iris metastasis can produce uveitis + hyphema + secondary glaucoma.
• Scirrhous breast carcinoma can cause orbital enophthalmos, rather than the more usual proptosis.
• On ultrasound, metastases generally have moderate-to-high internal reflectivity, whereas melanoma classically has lower reflectivity.
• Ocular metastasis generally signifies advanced systemic metastatic disease, so systemic restaging is essential.