Ocular Tumors Table of Contents Eye Anatomy Types of eye tumors What are the benign tumors that occur in the eye? Are there tumors that spread to the eye from cancers in other parts of the body? What kind of testing will be done to diagnose the type of tumor in my eye? What tests are done to find out if the tumor has spread to other parts of my body? Can I be assured the cancer has not spread to other parts of my body if the results from all the testing are normal? What are the different size classifications of tumors, and how are they treated? What are the complications that occur from radioactive plaque therapy? Are there special concerns related to the emission of radiation while the plaque is on my eye? How will I know if the radiation killed the tumor? What if the tumor continues to grow? How often will I need to see the doctor after radiation treatment? How is enucleation performed? How will I see with one eye if my fellow eye is removed? Why isn’t a biopsy done to make the diagnosis of melanoma? Will the cancer spread to my other eye? Why was I sent to Retina Associates of Florida for my condition?

Eye Anatomy
A brief review of eye anatomy is necessary to understand the cause and nature of eye tumors. The eye is a spherical structure, a little smaller than a golf ball, that is composed of fibrous tissue, vascular tissue, muscle, pigment cells, secretor cells and nervous tissue called the retina. The eye has three layers, like an onion, and each layer is composed of special tissues. The outside coat is the fibrous tissue, the front is transparent and is called the cornea and the side and back is white and is called the sclera. The sclera is covered by a membrane called the conjunctiva. Inside the sclera is the second layer that is called the uvea. The front includes the iris or the colored part of the eye. The pupil is not a structure at all, but is the absence of the iris. Peripheral to the iris is the ciliary body and muscle that secretes fluid that maintains eye pressure, a muscle that allows the eye to change focus (accommodate). In the back of the eye is a vascular layer called the choroid that provides nutrients to the retina. It also contains pigment cells to reduce light scatter in the eye. These pigment cells are derived from the same embryonic layer as the pigment cells in the skin (the neural crest). These pigment cells are the source of melanomas that affect the eye. Lastly, the innermost layer is a neural tissue that is called the retina. This neural tissue connects to the brain along the optic nerve.

The choroid has the highest blood flow per weight of tissue and is therefore a common site of metastasis from other cancers. The most common cancers that spread or metastasize to the eye are breast cancers and lung cancers. Sometimes cancers of the lymphoid tissue (lymphoma) may be present in the vitreous or under the retina.

The retina is the site of a special hereditary tumor that is seen in infancy and early childhood that is known as a retinoblastoma. This is a highly malignant, often hereditary tumor, which is usually managed in special centers with expertise in pediatric oncology. Great progress has been made in the management of these tumors and while formerly retinoblastoma led almost universally to death, now the survival rate is very high.

There is also a group of benign retinal tumors seen in patients with other genetic tumor abnormalities. These include angiomas, hemangiomas, fibromas, adenomas and myomas. The most common tumors that we see in the adult population are melanomas in the choroid, iris or ciliary body; tumors that are metastatic to the eye; and vascular tumors known as hemangiomas. We are next going to review the tests we use to evaluate ocular tumors, and then we will review each special type of tumor with special attention to pigmented tumors, including melanoma.

Types of Eye Tumors
All tissues in the eye, except the lens, may develop benign or malignant tumors. A benign tumor is one that grows locally, but does not spread. Even though it does not spread to other organs, it can cause local damage to important structures and can lead to loss of vision in the affected eye. Malignant tumors of the eye are serious and even life-threatening medical problems. Malignant tumors can spread throughout the body and can cause death. The most common tumors that we see in the adult population are melanomas in the choroid, iris or ciliary body; tumors that are metastatic to the eye; and vascular tumors known as hemangiomas.

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What are the benign tumors that occur in the eye?
Benign tumors of the eye are called nevi (plural of nevus). Most people have some nevi or moles on their skin. About seven percent of Caucasians will have one or more identifiable nevi in their eye. In typical cases, nevi can usually be differentiated from melanomas. Sometimes the appearance of the pigmented tumor does not clearly fit into the benign or malignant category. When this happens on the skin, the dermatologist usually takes a biopsy for microscopic examination by a pathologist. For ocular tumors, biopsies are difficult and can be dangerous to vision. We therefore try to differentiate benign and malignant tumor without a biopsy. For these tumors of uncertain malignancy, regular follow-up (which may include photography and ultrasonography) is important to make sure they do not undergo cancerous changes.

Choroidal hemangioma is a benign tumor that occurs posteriorly in the eye and is often confused with melanoma. It is diagnosed reliably by standardized ultrasound and ICG dye angiogram. For patients who have visual loss, there is a new treatment called Photodynamic Therapy. This is a special form of treatment using a laser-activated drug that was developed for the treatment of macular degeneration. It has also been shown to work extremely well in treating blood vessel tumors like hemangioma.

Are there tumors that spread to the eye from cancers in other parts of the body?
Metastatic tumors are tumors that spread to the eye from another cancer elsewhere in the body. The choroid has the highest blood flow per weight of tissue and is therefore a common site of metastasis from other cancers. They are the second most common eye tumor seen in clinical practice. They are usually treated by external beam radiation or observation if the patient is undergoing chemotherapy. Most often, the drugs used in chemotherapy for the primary cancer will also cause the eye tumor to shrink. The most common tumors that spread to the eye are from lung and breast cancers.

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What kind of testing will be done to diagnose the type of tumor in my eye?
There are numerous types of tests that may be prescribed. They are explained below:

1. Photography is routinely performed with a special camera that allows us to document the size and margins of a lesion. It is most important when lesions of uncertain malignancy are followed with serial observation. Changes in size and margins may indicate a malignant nature of the lesion.
   
2. Ocular Ultrasound is the most useful diagnostic tool used to evaluate and measure ocular tumors. Special ultrasound techniques evaluate the internal consistency of a tumor to help separate blood vessel tumors, metastatic tumors and primary melanomas. Serial ultrasound measurements are the most reliable way to see if a tumor is growing in thickness and to measure response to therapy.
   
3. OCT is a special test to measure retinal thickness. It may help in differentiating benign from malignant tumors. What tests are done to find out if the tumor has spread to other parts of my body? The most common spread of ocular melanoma is to the liver or lung. These organs are carefully screened at the time of diagnosis of the eye tumor and in follow-up, especially during the first five years following treatment. Routinely, PET/CT scans are done combined with blood tests checking liver enzymes. PET scanning combined with CT is the most recent advance in body imaging. It has been shown to be very sensitive in finding metastatic melanoma. Typically, a PET/CT scan is ordered for patients who have large and medium tumors for which treatment is being planned, but not for small tumors under observation. A chest x-ray is usually performed as well.

What tests are done to find out if the tumor has spread to other parts of my body?
The most common spread of ocular melanoma is to the liver or lung. These organs are carefully screened at the time of diagnosis of the eye tumor and in follow-up, especially during the first five years following treatment. Routinely, PET/CT scans are done combined with blood tests checking liver enzymes. PET scanning combined with CT is the most recent advance in body imaging. It has been shown to be very sensitive in finding metastatic melanoma. Typically, a PET/CT scan is ordered for patients who have large and medium tumors for which treatment is being planned, but not for small tumors under observation. A chest x-ray is usually performed as well.

Can I be assured the cancer has not spread to other parts of my body if the results from all the testing is normal?
Although it is a very good sign, normal test results do not guarantee that there has not been a microscopic spread of tumor cells.

What are the different size classifications of tumors, and how are they treated?
In cases where the tumor is most likely benign, observation is usually the chosen management. Photographs and ultrasound measurements will be taken of the suspicious area, and the patient is followed at frequent intervals until growth or absence of growth is determined. Several studies have shown only minimal risk in management by careful observation of small pigmented lesions. The operative word there is careful observation! Depending on the individual characteristics of the lesion, about 21% will show growth after two years of observation. Small tumors are defined as 1 to 2.5 millimeters in thickness. If definite growth is observed, the tumor is classified as melanoma, and the standard approach is treatment with radioactive therapy. Melanoma-related mortality is only one percent at five years in carefully treated and observed small tumors. Other options for treatment include enucleation (removal of the eye), and a form of laser treatment called Transpupillary Thermotherapy (TTT). Rarely, other treatments have been tried or are under investigation.

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What are the different size classifications of tumors, and how are they treated?
Medium melanomas are defined as being 2.5 to 10 millimeters in thickness and up to 16 millimeters in diameter. Most medium melanomas are now managed by radiation therapy. Radiation treatment was started forty years ago in Great Britain. Radiation therapy is done either by brachytherapy using Iodine-125 implanted seeds or external beam therapy with high-energy particles. In brachytherapy, radioactive seeds are placed in a gold plaque and sewn onto the outside of the eye in a surgical procedure. The gold plaque with seeds is left in place on the eye for 5 to 7 days. In external beam therapy, the radiation is delivered by a machine and the patient goes for treatment to a radiation center several times and gets divided doses of radiation.

Visual results with radioactive plaque therapy depend on the size of the tumor and its location. The treatment of tumors close to vital structures is more likely to cause visual loss than tumors in the periphery. Visual loss occurs in 80% of eyes with 63% of eyes being legally blind, 20/200 or worse, at three years after treatment. Local control of the tumor is achieved 95% of the time, and some vision is maintained most of the time.


For patients with medium-sized tumors, the five-year survival rate is 82 percent whether treated by enucleation or radiation.

What are the different size classifications of tumors, and how are they treated?
Proton Beam Therapy is a special form of external beam radiation that is performed in Boston, California, and soon in Jacksonville. Surgery is required to mark the margins of the tumor with the placement of rings that are visible on X-ray. After allowing the patient to recover from the surgery, the proton beam treatment is delivered as an out-patient usually over several days. The rings do not have to be removed and do not interfere with MRI scans, but are visible on X-ray and CT scans. This treatment is most often used for large tumors or tumors near the optic nerve.

Transpupillary Thermotherapy (TTT) is a form of laser surgery that heats the tumor causing destruction of the cancer. Some doctors have used it as single therapy, but there have been several cases reported where the tumor grew out of the back of the eye. It is now used as adjunctive therapy for tumor recurrences or for problems with management where the tumor is large, not responding to radiation, or where there is persistent subretinal fluid following treatment.

For large melanomas, measuring greater than 16 mm across at the base and thicker than 10 mm in height, the choices of treatment are surgical removal of the eye (enucleation) or proton beam radiation. Enucleation has been the traditional treatment for melanoma for many years. Enucleation is usually the best choice for patients with large tumors and a healthy second eye. The large amount of radiation required to eradicate the tumor causes blindness or poor vision in most cases. For special situations, there may be reasons to consider radiation therapy, but preserving good vision is rare in the treatment of large tumors. Enucleation offers rapid rehabilitation and certain tumor destruction.

For large tumors, external radiation using proton beams offers advantages over radioactive plaques, and we usually recommend it for patients with large tumors who don't want the eye removed. Proton beam therapy is available in Boston and California. Particle beam treatment is indicated for large tumors or tumors surrounding the optic nerve. The visual results for these large tumors and tumors around the optic nerve are poor, but the eye can be maintained. The University of Florida medical center in Jacksonville has constructed a proton beam facility in Jacksonville. It is currently in the process of initiating treatments. This form of therapy should be available soon in Florida. For patients with large tumors, the five-year survival rate for patients who had enucleation was 60 percent. Clearly, treating smaller tumors gives better results than treating large tumors.

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What are the complications that could occur from radioactive plaque therapy?
This type of radiation therapy does not cause the patient to feel bad or the hair to fall out. Sometimes during surgery, the ocular muscles have to be moved around the eye so double vision may occur immediately following the surgery. When the plaque is removed (after 5-7 days), the muscles are replaced to their natural position and this usually takes care of the double vision.

Are there special concerns related to the emission of radiation while the plaque is on my eye?
During treatment, the patient may usually go home but needs to stay away from young children or women of child-bearing age. Patients should plan on isolating themselves from the general public while the plaque is in place. Caution should be exercised by those caring for the patient to keep a 6-foot distance whenever possible (driving in a car with the patient in the back seat on the right side, sleeping in another bed, etc). To put it in perspective, with the above considerations, caretakers receive an amount of radiation approximately equal to one chest X-ray.

How will I know if the radiation killed the tumor?
Radiation is intended to stop the growth of the tumor. As long as the tumor stays the same size or shrinks, radiation is considered successful. Just as melanomas are thought to grow slowly, they usually shrink slowly, over several years. Sometimes they disappear completely, but this is not necessary for the treatment to be considered a success.

What if the tumor continues to grow?
Very rarely, there is persistent fluid or growth. In these cases, more treatment is needed. Radiation may be performed again, or other intervention may be necessary.

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How often will I need to see the doctor after radiation treatment?
The eye is examined postoperatively on several visits to make sure there are no surgical complications. Approximately three to six months after surgery, the tumor will be evaluated with an examination by the doctor, photography and ultrasound. This procedure is completed approximately every six months for 5 years. At the 5 year mark, follow up exams may be done once a year, instead of every six months.

How is enucleation performed?

Enucleation
Enucleation surgery is done in the hospital usually under general anesthesia. The eye is removed surgically, and the muscles of the eye are sewn over the prosthesis or to specially designed prostheses so there can be some movement of the "glass eye." The patient can usually go home after surgery and postoperatively there is usually not much pain. The prosthesis has two parts. There is an implant that is placed in the socket to replace the eye volume and a second part that can be taken in and out that looks like an eye. This second part is fitted about one month after surgery by a professional known as an ocularist. He paints a custom prosthesis to match your fellow eye. Most people are not able to recognize whether or not you are wearing a glass eye or have a natural eye.

How will I see with one eye if my fellow eye is removed?
Although there is a period of adapting to vision with one good eye, a return to normal living is possible. As a reminder, the loss of an eye later in life didnÕt cramp the style or detract from the achievements of some world-famous people in a variety of fields. To assist you with overcoming the difficulties associated with the loss of an eye, there is a book addressed primarily to the newly "one eyed." This guide is titled "A Singular View, the Art of Seeing with One Eye," authored by Frank Brady.

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Why isn't a biopsy done to make the diagnosis of melanoma?
With the current ocular testing done in the office and blood tests and scans done on the body, diagnostic accuracy in ocular melanoma is around 99% without biopsy. Fine needle biopsy is usually safe, but there is a theoretical risk of causing the tumor to spread or causing loss of vision. That is why it is rarely done, except in special circumstances. This procedure would be performed in the hospital.

Will the cancer spread to my other eye?
Ocular melanoma does not spread from one eye to the other.

Why was I sent to Retina Associates of Florida for my condition?
Drs. Grizzard and Hammer have many years of experience in diagnosing and treating lesions and tumors in the eye. Not only are they retina specialists, they have a sub- specialty in treating ocular tumors. They participated in the Collaborative Ocular Melanoma Study (COMS) for 18 years. COMS was a research program conducted through Johns Hopkins University with multiple clinical centers throughout the United States. The information gathered from this research guides their treatment for melanoma today. Many of the statistics quoted in this brochure were derived from the over 2,500 patients who were followed in this program, some of whom were treated at Retina Associates of Florida.

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