Eye cancers

ALSO KNOWN AS: Intraocular cancers, uveal cancers

RELATED CONDITIONS: Retinal detachment, angle-closure glaucoma

DEFINITION: Eye cancers are malignant tumors of the eye made up of the globe, orbit, and adnexal structures. The globe (or eyeball) is filled with a fluid called vitreous humor and contains the retina and the uvea. The uvea consists of the iris (pigmented area surrounding the pupil), choroid (pigmented lining of the eyeball that brings blood to the retina and the front of the eye), and ciliary body (made up of the cells producing the aqueous humor and the muscles that control the shape of the lens). Cancers that develop globally (retina and uvea) are called intraocular cancers. The orbit comprises the tissues surrounding the eyeball, including the muscles that control the directional movement of the globe and the nerves of the eye. Tumors in these tissues are called orbital cancers. The adnexal structures consist of the eyelids and the tear glands. Cancers that occur in these structures are called adnexal cancers.

Risk factors: For intraocular melanoma, the risk factors include advanced age (the peak age is seventy), being White, having light (blue or green) eye color, fair skin, and the ability to tan. For retinoblastoma in children, 10 to 15 percent of patients may have retinoblastoma in their family history. Mutations in the RB1 gene, which pass between generations, cause most retinoblastoma cases. If the disease passes from parent to child, the child often has retinoblastoma in both eyes.

Etiology and the disease process: The most common intraocular or uveal eye cancers are melanomas, although these are rare, with approximately 4.3 new cases per 1 million people. Most intraocular melanomas initially do not cause any symptoms, but as the tumor grows, symptoms may include distortion of the pupil, blurred vision, and decreased visual acuity caused by secondary retinal detachment. Extensive retinal detachment can be accompanied by secondary angle-closure glaucoma. Other tumors that can resemble intraocular melanomas in clinical presentation are metastatic carcinoma, posterior scleritis, and tumors such as nevi and hemangiomas. This should be considered when making a diagnosis of intraocular melanoma.

Most intraocular melanomas occur in the choroid and are called choroidal melanomas. Choroidal melanomas are primary intraocular cancers, that is, cancers that originate in the eye. They initiate from pigmented cells in the choroid and have the potential to become malignant (metastasize to other organs). The remaining intraocular melanomas are melanomas of the iris. These tumors often grow from pigmented spots in the iris that may be present for many years before developing into tumors. They are relatively slow-growing and rarely metastasize and, therefore, are associated with a better prognosis than choroidal melanomas.

Another kind of intraocular cancer is intraocular lymphoma, which can be either Hodgkin disease or non-Hodgkin lymphoma. These lymphomas typically originate in the lymph nodes but can also originate in the stomach, lungs, and eye. Primary intraocular lymphomas are rare and are always of the non-Hodgkin type. These cancers usually occur in older adults or individuals with comprimised immune systems.

Adnexal tumors affecting the eyelid include basal cell carcinomas, squamous cell carcinoma, sebaceous cell carcinoma, and malignant melanoma. Basal cell carcinomas and squamous cell carcinomas are most common in older adults with fair skin. Basal cell carcinomas commonly occur in the inner part of the lower eyelid and are often nodular, appearing as raised pearly bumps with tiny blood vessels. Sebaceous cell carcinomas originate in the eyelid tear glands in older adults and can be highly malignant, returning after removal and invading the eye socket and lymph nodes. Malignant melanomas are associated with unusual or changing pigmentation. Tumors of the conjunctiva can be squamous cell carcinoma, malignant melanoma, or lymphoma.

Secondary intraocular cancers originate in other organs in the body and spread (metastasize) to the eye. Breast and lung cancers are most likely to metastasize to the eye, especially the uvea. Tumors can also metastasize from the prostate, kidneys, thyroid, and the gastrointestinal tract, though this occurs less frequently than metastasis from the breast and lung.

Retinoblastoma is the most common form of eye cancer in children. It is most common in children younger than five and affects both sexes equally. Approximately three out of four retinoblastoma cases are unilateral (affecting one eye). About 90 percent of patients do not have a family history of retinoblastoma.

Incidence: About 3,500 adults are diagnosed with cancer of the eye and orbit each year, and around 350 die of the tumor. The incidence of intraocular melanomas, the most common form of intraocular cancer, is approximately five new cases per one million people annually. Globally, around 8,000 children are diagnosed with retinoblastoma annually, and in the United States, two to three hundred children are diagnosed annually. It affects all races with similar frequency.

Symptoms: Intraocular tumor symptoms include pupil distortion, blurred vision, bulging eyes, watery eyes, pain in or around the eye (rare), and decreased visual acuity caused by secondary retinal detachment. Extensive retinal detachment may be accompanied by secondary angle-closure glaucoma. Other symptoms may include floaters, where spots, flashes, or wavy lines appear in the visual field; loss of peripheral vision, where objects to the side cannot be seen; and a pigmented spot on the iris that enlarges with time (this could be a sign of iris melanoma). Symptoms of retinoblastoma include a white pupil reflex (leukocoria or cat’s-eye reflex) instead of the normal black pupil or red reflex.

Screening and diagnosis: Diagnosis of eye tumors can be performed using an eye examination with an ophthalmoscope or slit lamp. This is the single most important diagnostic test for eye tumors. For example, most choroidal melanomas can be diagnosed by visually examining the pupil for the presence of tumors. Choroidal melanomas range in shape and pigmentation from dark brown to unpigmented. However, most choroidal melanomas are brown to gray-green and have a dome or nodular shape.

Other tumors may need additional tests, which include echography or ultrasound, in which sound waves are directed at the eye from a small probe placed on the eye. The reflection patterns are then analyzed to determine if tumors are present. Another diagnostic technique is called fluorescein angiography, which involves introducing eye drops that cause pupil dilation. This is followed by injecting a fluorescent dye into a vein in the arm. The dye passes through the blood vessels in the back of the eye, and a camera takes photographs from which the physician can determine if a tumor is present. Echography and fluorescein angiography can also distinguish between eye tumors and hemorrhages or microaneurysms that may occur in the choroid or below the retinal epithelium.

The most invasive diagnostic test that can be performed is the eye biopsy. This involves inserting a long, narrow-bored needle into the eye and extracting tissue for examination with a microscope. The risk of ocular mortality associated with an eye biopsy, however, is a serious drawback to this diagnostic test and influences many physicians to use alternative means of diagnosis.

Staging of intraocular tumors involves determining the tumor thickness (apical height) and width (basal diameter). Tumor sizes are classified as small (apical height of 1 millimeter (mm) to 3 mm, basal diameter equal to or greater than 5 mm), medium (apical height of 2 mm to 10 mm, basal diameter less than 16 mm), large (apical height greater than 10 mm, basal diameter equal to or greater than 16 mm), and diffuse (horizontal, flat growth pattern and tumor thickness 20 percent or less than the greatest basal dimension). Diffuse tumors are rare and have a poorer prognosis. Physicians also determine if the tumor has metastasized and, if so, to what extent. Metastasis of the tumor to preauricular, submandibular, or cervical lymph node regions indicates that subconjunctival extension has occurred. Systemic metastasis usually occurs first in the liver and may occur in the lung, bone, and subcutaneous sites. Metastasis or spreading of the cancer to the optic nerve, eye socket, or meninges is rare and called extraocular extension. The American Joint Committee on Cancer has developed a method for intraocular cancer staging. Metastasis of retinoblastoma tumors is rare, but when it occurs, tumors can spread to the brain, central nervous system, and bones.

Treatment and therapy: One of the most commonly used methods of treating eye cancers is radiation therapy, which can shrink tumors but usually does not eliminate them entirely. It can take two formsplaque radiation therapy and external-beam, charged-particle radiation therapy. Plaque radiation therapy uses plaques with radioactive pellets on one side and gold coating on the other side. An is made in the conjunctiva, and plaques are sewn to the outside of the eye directly over the tumor, with the side coated with radioactive pellets facing the tumor. Plaque radiation therapy has a five-year control rate of more than 90 percent but has the disadvantage of a high risk of secondary cataracts. External-beam, charged-particle radiation therapy involves irradiating tumors with precisely focused radiation from a cyclotron, a piece of equipment that is available only at specialized centers. This type of therapy specifically kills tumor tissue without damaging surrounding healthy eye tissue and appears to have a control rate similar to that of plaque radiation therapy. The drawbacks are the need for specialized equipment with limited availability, the need for patient cooperation during the procedure (the eye needs to be held still so the radiation beam can be directed at the tumor), and the possibility of anterior-segment complications.

Other treatments include local tumor resection, which is used for ciliary body or anterior choroidal tumors with smaller basal dimensions and greater thickness. The eye tumor can also be treated with chemotherapy, which is administered intravenously and delivered to the eye through the bloodstream. If tumor treatment is unsuccessful, surgery may be required to remove the eye (enucleation). The empty eye socket can then be filled with a synthetic eyeball implant.

Modern treatments include with white light and laser radiation, transpupillary thermotherapy, and cryotherapy. Photocoagulation involves the destruction of small tumors by directing light through the pupil into the tumor. Photocoagulation techniques use a transscleral diode retinal photocoagulation (diopexy) probe that directs the light through the wall of the eye instead of through the pupil. This method can be used alone or together with plaque radiation therapy and cryotherapy. Cryotherapy involves applying a pen-like probe to the sclera just next to the tumor and freezing the tumor while the patient is under local or general anesthesia. This usually has to be repeated multiple times before the tumor is destroyed and can cause swelling of the eye and eyelids.

Prognosis, prevention, and outcomes: The prognosis of intraocular cancers depends on several factors, including cell type, tumor size, location of the anterior margin, the extent of ciliary body involvement, extraocular extension, and tumor recurrence. Cell type is the most commonly used factor for predicting cancer prognosis. Intraocular melanomas usually consist of spindle cells and epithelioid cells. Spindle cells have less potential for metastasis than epithelioid cells, and a tumor that is mostly made up of spindle cells is considered to have a better prognosis than one that consists mostly of epithelioid cells.

Recurrent melanoma always has a poor prognosis, regardless of cell type or stage. The treatment selected depends on the tumor size, age and health of the patient, site of recurrence, and previous treatment. The prognosis for retinoblastoma is usually very good, with nine out of ten children surviving to live normal lives.

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