Ciliary Body Melanoma and Its Molecular Genetics

What Is Ciliary Body Melanoma?

Ciliary body melanoma is also called uveal melanoma and is an uncommon type of eye cancer that originates from melanocytes (cells responsible for melanin production). This tumor primarily develops in the ciliary body, a component of the eye important for lens focusing. The risk factors of ciliary melanomas are somewhat similar to those of iris melanomas. Typically, the symptoms of this disease start appearing in the sixth decade of the affected individuals and manifest with visual symptoms.

What Is the Incidence of Ciliary Body Melanoma?

Ciliary body melanomas account for approximately 12 percent of all uveal melanomas. It accounts for about 5 to 10 percent of all melanoma incidents. It majorly affects adults in the age range of 40 to 70. Iris and ciliary body melanomas comprise about 15 percent of cases of ocular melanomas. Ciliary melanomas are frequently highly malignant and remain undetected as they are hidden behind the iris. They can be detected only when they grow larger due to their location behind the iris. They can occasionally be identified accidentally.

What Is the Molecular Genetics Behind This Disease?

Ciliary body melanoma, like other melanomas, involves various genetic changes and molecular pathways at the molecular level. Following are some of the important aspects to consider regarding the molecular genetics of this disease, ciliary body melanoma :

1. GNAQ and GNA11 Mutations: The majority of ciliary body melanomas exhibit activation if a mutation in GNAQ or GNA11 genes. These mutations will lead to continuous activation of signaling pathways, including MAPK or ERK and PI3K or AKT, as these are crucial for cell growth and survival.

2. Chromosome 3 Alteration: Ciliary body melanoma frequently exhibits alterations in chromosome 3, such as partial deletion or monosomy (loss of one copy). Ciliary body melanoma associated with the loss of chromosome 3 can have a poor prognosis, and there can be an increased risk of metastasis.

3. BAP1 Mutations: BAP1 (BRCA1-associated protein 1) is a type of tumor suppressor gene that is commonly mutated in uveal melanomas, which includes ciliary body melanoma also. BAP1 mutations are linked to poor prognosis and a high risk of spread.

4. SF3B1 Mutations: A subset of ciliary body melanoma has been associated to have mutations in the SF3B1 gene. SFB31 gene is associated with RNA splicing, and mutations in this gene can have distinct molecular and clinical features.

5. Others: Other gene mutations associated with ciliary body melanoma include EIF1AX, CYSLTR2, and PLCB4. These mutations are less prevalent compared to the frequent gene mutation involving GNAQ and GNA11 genes.

What Are the Clinical Manifestations of Ciliary Body Melanoma?

During the initial stages of the disease, ciliary body melanoma may not exhibit any noticeable symptoms. As the tumor progresses or when the disease gets severe, there can be the following symptoms:

• Blurred Vision: Tumor in the ciliary body can hinder normal vision leading to decreased vision or blurring.

• Visual Disturbances: Patients usually experience visual disturbances such as floaters (specs or spots that swiftly drift across the eye), flashing lights, and shadows in vision.

• Pupil Changes: Alterations in size and shape of the pupil, such as irregular constriction or dilation.

• Eye Discomfort: When the tumor grows larger in size, there can be a feeling of pressure, eye pain, and eye discomfort.

• Redness or Inflammation: In rare cases, ciliary body melanoma can cause redness or inflammation of the eyes.

How Is It Diagnosed?

Diagnosis of ciliary body melanoma can be challenging as the lesion can be easily overlooked. Uveal effusion (a syndrome causing exudative detachments of the retina, ciliary body, and choroid) might pose diagnostic difficulties, but imaging techniques and recent advancements can help in overcoming such obstacles. A comprehensive eye examination is performed by an ophthalmologist to diagnose ciliary body melanoma. In this evaluation, the pupil is dilated to inspect the region at the back of the eye.

Imaging tests like ultrasound, OCT (optical coherence tomography), and fluorescein angiography will help in assessing the tumor's characteristics, like location, size, and others. Incisional and excisional biopsy and FNAC (fine-needle aspiration) techniques will be helpful. Genetic profiling to determine metastasis. Investigation to determine if there is systemic involvement. Major investigations carried out by an ophthalmologist include:

• Three-Mirror Contact Lens Examination: The three-mirror contact lens is a specialized type of ophthalmic lens that incorporates three mirrors that are set at three different angles. They are applied directly into the patient’s eye using a coupling agent such as a viscous gel or saline solution, assisting with stability and placement of the lens. This helps in a comprehensive examination of the peripheral retina and optic nerve head.

• Binocular Indirect Ophthalmoscopy: This technique provides a wide view of the retina without contacting the patient’s eye. It is used to examine the posterior segment of the eye.

• Ultrasonic Biomicroscopy: It is a non-invasive diagnostic procedure that uses high-frequency ultrasound waves that will help produce clear cross-sectional images of the eye’s anterior segment. They provide real-time imaging and provide images that cannot be obtained by other imaging techniques like OCT.

• Gonioscopy: It is a diagnostic procedure carried out to detect angle invasion. They help in examining the angle drainage of the eye, as this is an important structure in the eye that is responsible for maintaining intraocular pressure and fluid outflow.

What Is the Treatment Protocol for Ciliary Body Melanoma?

The following are the treatment methods recommended for ciliary body melanoma :

1. Iridocyclectomy: This is also known as sclerouvectomy and is useful in small or medium-sized tumors that involve less than one-third of the angle. This procedure can have complications like retinal detachment, cataracts, vitreous hemorrhage, hypotony, lens subluxation, and incomplete resection.

2. Enucleation: It is necessary in case of large tumors.

3. Radiotherapy: This is done through proton beam irradiation or brachytherapy.

4. Systemic Treatment: This is indicated when the systemic spread is evident.

Conclusion:

The prognosis of ciliary body melanoma depends on various factors like the tumor’s size and location. The ideal treatment for ciliary body melanoma includes intervention in the early stages of intraocular disease before there is metastasis. Patients affected with ciliary body melanoma require frequent follow-ups even after treatment with an ocular or medical oncologist. They will survey any changes or metastasis of the tumor and provide an appropriate treatment plan. Gene profiling helps in identifying the molecular characteristics of the cancer and thereby provides information on therapeutic targets to reduce its progression.