Comprehensive Management of Choroidal Metastasis in Cancer Patients

Choroidal Metastasis: Diagnosis, Management, and Innovative Treatments

Choroidal metastasis is the most common form of intraocular malignancy, occurring when cancer cells from a primary tumor elsewhere in the body spread to the choroid, the vascular layer of the eye. Though uncommon compared to systemic metastasis, it is a significant concern for patients with advanced malignancies, particularly breast and lung cancers, which are the most frequent culprits. Choroidal metastases can lead to serious visual impairment, necessitating timely diagnosis and treatment to preserve vision and manage the underlying cancer.

This article provides an in-depth exploration of choroidal metastasis, including its diagnosis, management, and emerging treatment options.

Understanding Choroidal Metastasis

Choroidal metastasis occurs when cancer cells from primary tumors elsewhere in the body travel through the bloodstream and implant in the choroid. The choroid’s rich vascular supply makes it a prime target for metastatic cancer cells.

Epidemiology and Risk Factors

• Prevalence: Choroidal metastasis is the most common intraocular malignancy, accounting for roughly 88% of all ocular metastatic lesions.
• Primary Cancers: The majority of choroidal metastases arise from breast cancer in women and lung cancer in men. Other cancers known to metastasize to the choroid include gastrointestinal malignancies, prostate cancer, renal cell carcinoma, and cutaneous melanoma.
• Bilateral Involvement: Up to one-third of cases may present with bilateral metastases, making it important to evaluate both eyes during diagnostic workup.

Pathophysiology

Choroidal metastasis occurs when malignant cells from a primary tumor enter the bloodstream and are seeded into the choroidal circulation. Once in the choroid, these cells grow and form tumors that can disrupt the normal architecture and function of the eye. The predilection for the choroid over other ocular structures is largely due to its rich blood supply, which allows circulating cancer cells to lodge and proliferate in the vascular layer.

Metastatic lesions in the choroid are often yellowish-white in appearance and tend to be flat or minimally elevated, unlike primary choroidal tumors, which may be dome-shaped. These metastatic lesions can vary in size and cause a range of symptoms depending on their location and size.

Clinical Presentation of Choroidal Metastasis

Patients with choroidal metastasis often present with visual symptoms, though some may be asymptomatic, particularly in early stages. The clinical presentation can depend on the size and location of the metastasis as well as any associated complications.

Common Symptoms

• Blurred vision: The most frequent symptom, blurred vision, occurs as the metastatic lesion disrupts the normal retinal architecture or causes fluid accumulation under the retina.
• Metamorphopsia: Patients may report distorted vision (metamorphopsia) if the metastasis affects the macula, the central part of the retina responsible for sharp, detailed vision.
• Scotoma: Some patients experience scotomas (blind spots) in their visual field, which may progress if the lesion grows.
• Photopsia: Flashes of light (photopsia) can occur when the tumor causes retinal traction.
• Pain: While rare, pain may occur in advanced cases, particularly if the tumor invades the sclera or increases intraocular pressure.

Asymptomatic Presentation

In some cases, choroidal metastasis is detected during routine ophthalmologic examinations, particularly in patients already undergoing treatment for systemic cancer. Regular eye examinations are essential for cancer patients, especially those with known metastasis risk, as early detection of choroidal involvement can prevent more severe vision loss.

Diagnosis of Choroidal Metastasis

Accurate diagnosis of choroidal metastasis requires a comprehensive approach that includes clinical examination, imaging studies, and sometimes biopsy or molecular testing to confirm the nature of the lesion.

1. Fundoscopic Examination

The first step in diagnosing choroidal metastasis is a thorough dilated fundus examination. The characteristic appearance of choroidal metastasis includes:

• Yellow-white flat lesions: These lesions are often slightly elevated but less prominent than primary ocular tumors like choroidal melanoma.
• Associated retinal detachment: Many patients present with serous retinal detachment, particularly when the lesion is large.
• Location: Metastatic lesions are typically located in the posterior pole of the eye, though they can occur anywhere in the choroid.

2. Optical Coherence Tomography (OCT)

Optical coherence tomography (OCT) provides high-resolution cross-sectional images of the retina and underlying structures. OCT is particularly useful in identifying retinal changes associated with choroidal metastasis, such as subretinal fluid accumulation, retinal detachment, or disruption of the photoreceptor layer.

3. Ultrasound (B-Scan)

B-scan ultrasonography is a valuable tool for evaluating the size, shape, and internal reflectivity of the lesion. Choroidal metastases typically appear as low-to-medium reflective, flat, or dome-shaped masses. Unlike choroidal melanoma, which often exhibits higher reflectivity, choroidal metastasis is more homogeneous on ultrasound.

4. Fluorescein Angiography (FA) and Indocyanine Green Angiography (ICG)

Fluorescein angiography (FA) can highlight the vascular nature of the metastasis, often showing early hyperfluorescence with leakage in the later stages. Indocyanine green angiography (ICG) is particularly useful for detecting deeper choroidal involvement and may show abnormal vasculature not evident on FA.

5. Systemic Workup

Given that choroidal metastasis usually arises from a primary tumor elsewhere in the body, a systemic evaluation is necessary. This may include:

• CT or MRI scans: These imaging modalities can help identify the primary tumor and evaluate the extent of systemic metastasis.
• Positron Emission Tomography (PET) scans: PET scans can detect metastasis throughout the body, helping clinicians to locate the primary tumor if it is unknown at the time of ocular presentation.

6. Biopsy

While not always required, fine needle aspiration biopsy (FNAB) may be performed if the diagnosis is uncertain or if the lesion has atypical features. Cytological analysis of the biopsy sample can confirm the metastatic origin of the lesion, and molecular testing may provide insights into the tumor’s characteristics, such as receptor status in breast cancer metastasis.

Management of Choroidal Metastasis

The management of choroidal metastasis is multifaceted, involving local ocular treatment to preserve vision and systemic therapy to control the primary cancer and prevent further metastasis. The choice of treatment depends on several factors, including the size and location of the metastasis, the patient’s visual symptoms, and the prognosis of the underlying malignancy.

1. Observation

For small, asymptomatic choroidal metastases, particularly in patients with a limited life expectancy or stable systemic disease, observation may be an appropriate option. Regular monitoring with fundus photography, OCT, and ultrasonography is essential to detect any changes in the size of the lesion or the development of retinal detachment.

2. Radiotherapy

Radiotherapy is one of the most effective treatments for choroidal metastasis, particularly for patients with symptomatic lesions. Radiation can reduce the size of the tumor, resolve subretinal fluid, and improve or stabilize vision.

• External beam radiation therapy (EBRT): This is the most commonly used form of radiotherapy for choroidal metastasis. EBRT delivers a high dose of radiation to the tumor, effectively shrinking the lesion while minimizing damage to surrounding tissues. Common side effects include radiation retinopathy and cataract formation.
• Plaque brachytherapy: In select cases, plaque brachytherapy may be used. This technique involves placing a radioactive plaque on the sclera, directly over the metastasis. While commonly used for primary intraocular tumors like melanoma, it can also be used for metastases, though EBRT remains the more common choice.

3. Systemic Chemotherapy

Given that choroidal metastasis is often part of a wider metastatic process, systemic chemotherapy is an important component of treatment. Chemotherapy is directed at controlling the primary cancer and its spread, which in turn can lead to regression of the ocular metastasis.

• Breast cancer: In patients with breast cancer metastasis, hormone receptor status and HER2 status often guide treatment. Patients with hormone receptor-positive disease may benefit from endocrine therapy, while HER2-positive patients can receive targeted therapies like trastuzumab.
• Lung cancer: In patients with lung cancer metastasis, treatment typically includes platinum-based chemotherapy or targeted therapies depending on genetic mutations (e.g., EGFR, ALK mutations).

4. Immunotherapy

Immunotherapy has emerged as a promising treatment for many cancers, and it is increasingly being used in metastatic cancers, including those with ocular involvement. Checkpoint inhibitors, such as nivolumab and pembrolizumab, are being used to treat lung cancer and other malignancies that metastasize to the choroid.

• Checkpoint inhibitors: These drugs help the immune system recognize and attack cancer cells. Early studies show promise in using checkpoint inhibitors for choroidal metastases secondary to cancers such as lung cancer and melanoma.

5. Targeted Therapy

For cancers with specific genetic mutations or receptor targets, targeted therapy can be a highly effective treatment for choroidal metastasis.

• HER2-positive breast cancer: Targeted therapies such as trastuzumab and pertuzumab are effective in treating HER2-positive breast cancer, and they can lead to the regression of choroidal metastasis as part of systemic cancer control.
• EGFR or ALK-positive lung cancer: Patients with lung cancer harboring EGFR mutations or ALK rearrangements may benefit from targeted therapies such as osimertinib (for EGFR mutations) or alectinib (for ALK rearrangements).

6. Anti-VEGF Therapy

Anti-VEGF therapy has become a cornerstone of treatment for retinal vascular diseases, and its use has expanded to treat ocular complications of choroidal metastasis, particularly in cases with associated macular edema or serous retinal detachment.

• Intravitreal injections of anti-VEGF agents (such as bevacizumab or ranibizumab) can reduce vascular leakage, resolve subretinal fluid, and improve visual outcomes. This therapy is typically used in combination with systemic treatment or radiotherapy.

7. Surgical Intervention

Surgery is rarely required in the management of choroidal metastasis, but in cases of persistent retinal detachment or severe ocular complications, pars plana vitrectomy (PPV) may be performed. This procedure can remove subretinal fluid and reattach the retina, though it is generally reserved for complex cases.

Innovative Treatments and Future Directions

The field of oncology is rapidly evolving, and new treatments for metastatic cancers, including choroidal metastasis, are continually being developed. Several innovative approaches are showing promise in the management of ocular metastasis.

1. Proton Beam Therapy

Proton beam therapy is an advanced form of radiation that allows for precise targeting of tumors with minimal damage to surrounding tissues. It is particularly useful for treating ocular tumors, including choroidal metastasis, where preserving vision is critical. Proton therapy delivers highly focused radiation, making it an attractive option for patients with tumors near sensitive ocular structures such as the optic nerve or macula.

2. Personalized Medicine and Molecular Profiling

Advances in genomic profiling have transformed cancer treatment, allowing for personalized therapy based on the specific genetic mutations or molecular characteristics of a patient’s tumor. Molecular profiling of choroidal metastases can identify actionable mutations, guiding the use of targeted therapies or immunotherapies.

3. Liquid Biopsies

Liquid biopsy is a non-invasive diagnostic technique that detects circulating tumor DNA (ctDNA) in the blood. Liquid biopsies are being explored as a tool for monitoring the progression of metastatic cancer and detecting ocular metastasis earlier. This approach has the potential to revolutionize how we monitor cancer spread to the eye and other organs.

4. Gene Therapy

Gene therapy is an emerging field with potential applications in metastatic cancer treatment. Researchers are exploring the use of gene-editing techniques, such as CRISPR-Cas9, to target genetic mutations that drive cancer metastasis. While still in the experimental stage, gene therapy may one day offer a novel treatment approach for choroidal metastasis.

Prognosis and Long-Term Outcomes

The prognosis for patients with choroidal metastasis depends largely on the underlying primary cancer, the extent of systemic metastasis, and the response to treatment. In many cases, choroidal metastasis is a late-stage manifestation of cancer, and the overall prognosis is often poor. However, with advances in systemic therapies, including targeted treatments and immunotherapies, many patients can achieve improved survival and quality of life.

• Visual prognosis: The visual prognosis depends on the size and location of the metastasis, as well as the success of treatment in controlling the tumor and associated complications like retinal detachment.
• Systemic prognosis: The systemic prognosis is determined by the primary cancer and the extent of metastatic spread. Breast and lung cancers, which are the most common causes of choroidal metastasis, have varied prognoses depending on receptor status, mutation profiles, and response to systemic therapies.

Conclusion

Choroidal metastasis is a serious but treatable complication of systemic cancer. Advances in diagnostic imaging, radiation therapy, systemic treatments, and innovative therapies like proton beam therapy and immunotherapy are improving outcomes for patients with ocular metastasis. Early detection and a multidisciplinary approach to treatment are essential to preserving vision and managing systemic disease.