Innovations in Choroidal Metastasis Treatment

What is Choroidal Metastasis?

Choroidal metastasis is the spread of cancerous cells to the choroid, the vascular layer of the eye that sits between the retina and the sclera. Because the choroid is rich in blood vessels, it is a common site for metastatic tumors, particularly from primary cancers such as breast cancer, lung cancer, and, less frequently, cancers of the gastrointestinal tract, kidneys, and prostate. Choroidal metastasis is the most common type of intraocular malignancy, accounting for more cases than primary choroidal tumors.

Patients with choroidal metastasis frequently report blurred vision, visual field defects, flashes of light (photopsia), and, in some cases, pain if there is associated inflammation or increased intraocular pressure. These symptoms occur because the tumor can cause retinal detachment or thickening, resulting in visual disturbances. A thorough ophthalmic examination is usually required to make a diagnosis, which may include indirect ophthalmoscopy, ultrasonography, fluorescein angiography, and optical coherence tomography (OCT). In some cases, a biopsy may be required to confirm the diagnosis and determine the primary cause of the cancer.

Understanding choroidal metastasis is critical for both ophthalmologists and oncologists, as it frequently indicates an advanced stage of systemic cancer. Management of this condition necessitates a multidisciplinary approach that addresses both the ocular and systemic components of the disease. Timely diagnosis and intervention are critical for preserving vision and improving the overall prognosis for affected patients.

Conventional Management and Treatment for Choroidal Metastasis

The conventional approach to managing and treating choroidal metastasis focuses on controlling the primary cancer, alleviating ocular symptoms, and preserving vision. Treatment strategies are tailored to each patient’s specific condition, taking into account factors such as the type and stage of the primary cancer, the extent of ocular involvement, and the patient’s overall health.

Systematic therapy:

1) Chemotherapy: Systemic chemotherapy is frequently the primary treatment for choroidal metastasis, particularly when it is part of a larger disease. The type of primary cancer determines the appropriate chemotherapy drugs. Cyclophosphamide, doxorubicin, and paclitaxel are examples of agents used to treat breast cancer metastases. Chemotherapy can help shrink metastatic tumors and control systemic disease, alleviating ocular symptoms.

2. Hormonal Treatment: Hormonal therapies like tamoxifen, aromatase inhibitors, or androgen deprivation therapy can be effective for hormone receptor-positive cancers such as breast and prostate cancer. These treatments slow the progression of hormone-sensitive tumors and can reduce the size of choroidal metastases.
3. Targeted Therapy: Targeted therapies, which block specific molecules involved in cancer growth and spread, are becoming more popular in the treatment of metastatic cancer. Trastuzumab for HER2-positive breast cancer and tyrosine kinase inhibitors for lung cancer are particularly effective in lowering metastatic burden, including in the choroid.

Local Ocular Therapy:*

1. Radiation Therapy:** Localized radiation therapy is a popular and effective treatment option for choroidal metastasis. There are several types of radiation therapy:
   • External Beam Radiotherapy (EBRT): This technique employs high-energy beams to target metastatic tumors in the eye. It effectively reduces tumor size and alleviates symptoms.
   • Plaque brachytherapy: This involves applying a small radioactive plaque to the sclera over the tumor site. It delivers a large dose of radiation directly to the tumor while sparing the surrounding healthy tissues.

2) Laser Photocoagulation: This method involves using a laser to create small burns on the tumor, which aids in the sealing of leaking blood vessels and the reduction of retinal detachment. It is less commonly used for choroidal metastasis, but it can be effective in certain situations.

3. Intravitreal Injections: Anti-vascular endothelial growth factor (anti-VEGF) injections can help manage complications like macular edema and neovascularization. These injections, such as bevacizumab or ranibizumab, can enhance retinal health and vision.
4. Surgical Intervention: In severe cases of retinal detachment or other complications that cannot be treated with less invasive methods, surgical intervention may be required. This can include procedures such as vitrectomy, which removes the vitreous gel and reattaches the retina.

Supportive care:

1. Pain Management: Analgesics and anti-inflammatory medications are used to treat pain caused by choroidal metastasis, especially when there is inflammation or increased intraocular pressure.
2. Visual Aids: Patients with severe vision loss may benefit from visual aids and rehabilitation services to improve their overall quality of life.

Despite the fact that these conventional treatments are effective in many cases, managing choroidal metastasis presents several challenges, including the potential side effects of systemic therapy, the precision required in local treatments, and the need for a multidisciplinary approach. These factors highlight the significance of ongoing research and the development of novel treatments.

Innovative Therapies for Choroidal Metastasis

The treatment of choroidal metastasis is improving with the development of novel therapies and technologies aimed at increasing efficacy, lowering side effects, and providing more personalized treatment options. These advancements include new pharmacological agents, advanced radiation techniques, novel drug delivery systems, and emerging therapies that target metastasis’ molecular mechanisms.

**1. Immunotherapy:

Immunotherapy has transformed the treatment of cancer by using the immune system to combat cancer cells. Recent immunotherapy developments are being investigated for their potential in managing choroidal metastasis.

• Checkpoint Inhibitors: Pembrolizumab and nivolumab, two drugs that target immune checkpoints such as PD-1 and CTLA-4, have shown promise in the treatment of metastatic cancer. These agents stimulate the immune system to recognize and destroy cancer cells, including those in the choroid.
• CAR T-Cell Therapy: This novel approach involves modifying a patient’s T-cells to express chimeric antigen receptors (CARs), which target specific cancer antigens. CAR T-cell therapy has proven effective in treating certain hematologic malignancies and is being studied for solid tumors, including ocular metastases.

1. Advanced Radiation Techniques:

Radiation therapy remains a cornerstone in the treatment of choroidal metastasis, with advances in radiation technology improving its precision and efficacy.

• Proton Beam Therapy: Proton beam therapy provides precise tumor targeting while causing minimal damage to surrounding healthy tissues. This is especially useful for treating choroidal metastasis, where maintaining vision is critical. Proton therapy delivers high-dose radiation directly to the tumor, lowering the risk of radiation-related side effects.
• Stereotactic Radiosurgery (SRS): SRS employs highly focused radiation beams to treat small, well-defined tumours in a single session. This technique can accurately target choroidal metastases while minimizing exposure to adjacent ocular structures.

1. Gene Therapy:

Gene therapy is a new field that has the potential to revolutionize the treatment of choroidal metastasis by targeting the genetic abnormalities that cause cancer growth.

• Oncolytic Viral Therapy: This method employs genetically modified viruses to selectively infect and kill cancer cells while preserving normal cells. Oncolytic viruses can also cause an anti-tumor immune response. Early studies on the use of oncolytic viral therapy for ocular metastases have shown promise in preclinical models.
• CRISPR–Cas9: This gene-editing technology enables precise genome modifications, allowing researchers to target and disrupt cancer-related genes. CRISPR-Cas9 is being studied for its ability to correct genetic mutations and slow cancer progression, particularly in metastatic sites such as the choroid.

1. Targeted Drug Delivery:

Advances in drug delivery systems are improving the administration and efficacy of choroidal metastasis therapies.

• Nanoparticle-Based Delivery: Nanoparticles can encapsulate drugs and deliver them directly to the tumor site, increasing drug concentration while decreasing systemic toxicity. Researchers are working to create nanoparticle-based delivery systems for chemotherapy and targeted therapies for choroidal metastasis.
• Intervitreal Implants: Sustained-release intravitreal implants are being developed to deliver therapeutic agents directly to the eye over an extended period of time. These implants can release drugs over time, reducing the need for frequent injections and increasing patient compliance.

1. Personalized Medicine:

Personalized medicine tailors treatment to each patient’s unique characteristics, drawing on genetic, molecular, and clinical data.

• Genomic Profiling: Comprehensive genomic profiling of tumors can identify specific mutations and molecular alterations that promote cancer growth. This data can help guide the selection of targeted therapies and improve treatment outcomes for patients with choroidal metastases.
• Liquid biopsies: Liquid biopsies, which analyze circulating tumor DNA (ctDNA) in blood samples, provide a non-invasive way to track disease progression and treatment response. Liquid biopsies can detect genetic changes associated with metastasis, allowing for timely treatment adjustments.

6. Combined Therapies:

Combining different treatment modalities is a strategy that is gaining popularity in the treatment of choroidal metastases.

• Immunetherapy and Radiation: Combining immunotherapy and radiation therapy can increase the anti-tumor effects of both treatments. Radiation can increase tumor immunogenicity, making them more susceptible to immune-mediated destruction.
  Targeted Therapy and Chemotherapy: Combining targeted therapies with traditional chemotherapy can produce a synergistic effect, increasing treatment efficacy. This approach can treat both the primary tumor and metastatic sites, including the choroid.