Melanoma is not the only cancer that affects the eye. There are several other types of cancer, all of which are very rare. These can be devastating to patients and their families, to whom we at A Cure In Sight can offer valuable information and support.
Retinal Lymphoma is a cancer of a type of white blood cells, called lymphocytes, which tend to proliferate uncontrollably in the retinas and the brain to cause loss of vision and life-threatening disease.
This cancer usually develops in men and women older than 50 years unless the immune system is deficient, in which case it can develop at a younger age.
In the early stages, retinal lymphoma can resemble ocular inflammation (‘uveitis’) and all too often patients receive the wrong diagnosis and treatment for months or even years. The diagnosis is confirmed by vitreous biopsy, obtaining a sample of vitreous gel with an instrument known as a vitreous cutter (similar to a needle) and examining the specimen in a laboratory.
Ocular treatment usually consists of radiotherapy or repeated injections of chemotherapy into the eye. Sooner or later (sometimes even before the eye disease), lymphoma develops in the brain to cause very serious illness. Treatment of brain lymphoma (known as CNS lymphoma) has advanced in recent years, so that life expectancy has improved. Some centers therefore treat retinal lymphoma with systemic chemotherapy, possibly also including immunotherapy, in the hope of delaying or preventing the brain lymphoma.
Conjunctival Cancers, other than melanoma, include squamous cell carcinoma, lymphoma, and other rare types.
Squamous cell carcinoma tends to affect older individuals, men and women, and is caused by factors such as strong sunlight exposure and some papilloma viruses.
It often starts off by spreading across the surface of the conjunctiva, in the epithelium, and this stage is referred to as carcinoma in situ, similar to melanoma in situ or primary acquired melanosis (PAM) with atypia.
At any stage, the carcinoma can form a nodule and can spread deeply (i.e., ‘invasive carcinoma’). If neglected, this cancer can invade the tissues around the eye and even the eye itself. It can also metastasize through the blood vessels and lymph channels to glands in the neck and other parts of the body.
Carcinoma in situ usually responds to chemotherapy drops, such as 5-FU, mitomycin C and interferon. Invasive carcinoma usually requires surgical excision, possibly followed by a course of chemotherapy drops and/or radiotherapy to prevent the disease from recurring.
Retinoblastoma is a very aggressive cancer arising in the retina. It occurs when two mutations occur: one in the ‘retinoblastoma’ gene inherited from one parent and the other in the same gene inherited from the other parent. (The need for two mutations is known as the ‘two-hit hypothesis’).
When both mutations occur in the same retinal cell, then only one tumor develops in one eye. This is known as somatic retinoblastoma.
If the first mutation happens before birth or if it is inherited, then most or all cells in the body have that mutation, including the germ cells (i.e., sperm cells or eggs). This is known as germline retinoblastoma. Patients with a germline mutation tend to develop several retinoblastomas, usually in both eyes. They are also predisposed to cancers of the brain, bone, lung, and other organs. Each child born to these patients has a 50-50 chance of inheriting the disease.
Retinoblastomas develop in the first two years of life, sometimes even before birth. Often, the disease becomes obvious when a pupil turns white (‘leukocoria’) or when a squint develops or when it is noticed that the child cannot see properly. Unlike intraocular melanoma, biopsy is not safe because of the high risk of disseminating tumor cells outside the eye. The mutation is identified by analyzing a blood sample, buccal smear (from the lining of the mouth) or by harvesting the tumor itself after the eye is removed.
Treatment is very urgent and is selected according to the size, location and extent of any retinoblastomas, as well as their effects on the eye (e.g., glaucoma, retinal detachment). Most patients receive chemotherapy, which can be administered systemically, or into the artery behind the eye (through a very fine tube passed from the groin, through the heart and up the neck), or by injection into the vitreous gel of the eye, using a fine needle. Small tumors closer to the front of the retina can often be treated with cryotherapy (i.e., ‘freezing treatment’). Radiotherapy can itself cause cancer, especially in patients with germline retinoblastoma. It is therefore avoided if possible, unless the radiation can be focused only on the tumor with a radioactive implant or proton beam. If the tumor is very advanced it may be wise to remove the eye (i.e., enucleation), especially if the fellow eye is healthy.
Retinoblastoma treatment and investigation requires general anesthetics to be repeated every month until the age of two years, then at increasing intervals until the age of around five years, when the child can cooperate with eye exams. Exams are then needed every six months until the age of nine years, then once a year. Lifelong surveillance and education are required to avoid cancer triggers, such as sunburn, smoke and unhealthy diets. Genetic counseling is also needed because of the heritable nature of retinoblastoma.
Intraocular Metastasis arise from cancers of the breast, lung and other organs, reaching the eye through the blood circulation. These tumors can affect one or both eyes at the same time and often grow quickly, causing loss of vision.
Most metastases have a distinctive appearance, but some may require biopsy with a fine needle or a vitreous cutter to confirm the diagnosis. Many patients report concurrent or previous cancer, especially those with a primary breast tumor. Some patients are not aware of their extra-ocular malignancy, especially those with metastases from lung. In these patients, the primary tumor may be located only after extensive tests, such as scans of the chest, abdomen and pelvis.
Treatment is selected according to the type of cancer as well as the extent of the disease within the eye and in other parts of the body. If the patient is about to start systemic therapy, the doctor may wait and see how the ocular disease responds to such treatment before deciding on ocular radiotherapy and/or some form of laser treatment. Removal of the eye is rarely necessary, unless the eye has become irreversibly inflamed painful. The life expectancy of patients with intraocular metastasis has improved considerably in recent years, thanks to the therapeutic advances that have taken place and which are still ongoing.