As life expectancy continues to improve for many cancer patients, ophthalmologists increasingly will be called upon to identify ocular metastases. These are the most common ocular malignancies, with an estimated incidence of 30,000 cases per year (vs. about 2,500 cases of primary eye cancers). But many eye metastases go unrecognized.
“Many patients with metastasis to the eye never make it to the eye doctor,” noted Carol L. Shields, MD, associate director of and attending surgeon in the oncology service of Wills Eye Hospital in Philadelphia. “That’s because a little blurred vision does not seem important when they have so many other problems.”
But that may be changing, especially for patients with breast cancer. “For long-term breast cancer survivors, we’re clearly seeing people who present with metastatic disease to the eye and then go on to live another 10 years,” said Timothy G. Murray, MD, professor of ophthalmology and radiation oncology at the University of Miami. “So eye involvement is being recognized more often, and it’s becoming more critical
to care for these patients so that they can maintain good vision.”
Although tumors can metastasize to the lids, conjunctiva or orbit, the intraocular contents are by far the most common site. Cancers typically metastasize to the choroid, most often to the macular or perimacular region. Only rarely do they affect the iris, retina or optic disc. “If you look in the eye and see a creamy yellow, elevated mass deep to the retina in the choroid,” Dr. Shields said, “that should be very suspicious for a metastatic tumor.”
Patients typically present with a change in vision—visual loss from metamorphopsia or a change in visual field. Nonspecific symptoms, such as increased floaters or photopsia, are even more common. Some patients have no symptoms at all, and the lesions are discovered only on a dilated exam.
Identifying the Primary Site
Breast cancer is the most common tumor to metastasize to the eye, followed by lung cancer. Gastrointestinal, renal, prostate and skin cancers occasionally metastasize to the eye but account for a much smaller percentage of cases.
About 85 percent of patients with breast cancer metastases come in with a known history of breast cancer, Dr. Murray said. With lung cancer metastases, however, about two-thirds of patients don’t know they have cancer.
“When patients with a choroidal metastasis say they have no history of cancer, the first test you do is a chest x-ray because the lesion is much more likely to have originated from an undetected [case of] lung cancer,” Dr. Shields said. “Breast cancer patients give a different history. They usually say, ‘I had breast cancer 10 years ago, it recurred five years ago and now I can’t see.’
“When breast cancer metastasizes to the eye, it tends to be bilateral and multiple,” Dr. Shields continued. “Patients tend to get a shower of mets up one of the arteries to the brain. Some lodge in the choroid and others lodge in the brain. If you do a brain scan, you’ll find that about 40 percent of these patients also have brain metastases.”
Lung cancer metastases, in contrast, are rarely bilateral and multifocal. Moreover, they more often produce pain—sometimes unbearable pain—whereas most other metastases are painless.
Breast cancer metastases also must be differentiated from primary ocular melanomas. According to Dr. Shields, breast cancer metastases tend not to be very thick, measuring about 2 to 3 millimeters, vs. an average thickness of 5.5 mm for melanoma. Metastases also tend to be yellow and very homogeneous in appearance, and the overlying retinal pigment epithelium is not as disturbed as it often is with a melanoma.
Melanomas with the classic pigmentation or irregular coloration generally are not difficult to distinguish from a breast cancer metastasis. The differential diagnosis is more challenging with nonpigmented melanomas.
Not all ocular metastases fit the classic presentation of a creamy yellow mass deep to the retina. Less common presentations include a serous, nonrhegmatogenous retinal detachment with no apparent mass (flat metastasis), a swollen optic disc (optic nerve metastasis) or a hypopyon to the anterior chamber. Endophthalmitis also must be ruled out because many of these patients are on chemotherapy.
Metastasis Suspected: What Next?
Referral. Detection of a suspected ocular metastasis should prompt an immediate referral to an ocular oncologist or, if that individual is not available, to a retinal specialist. “The referring ophthalmologist doesn’t even have to be right about the diagnosis,” Dr. Murray said. “If they even think it’s a cancer, we’ll see the patient right away. We never say no to a patient.”
Examination. Patients receive a typical comprehensive exam, Dr. Murray said. Those with suspected metastasis to the choroid are given a dilated fundus exam with an indirect ophthalmoscope.
“Our patients are aggressively imaged after a lesion is established,” Dr. Murray said. “We use wide-field photographs, fluorescein angiography to rule out simulating lesions, ocular computed tomography if there is secondary macular involvement and, most important, A- and B-scan echography to evaluate the characteristics of the lesion and the associated anatomic involvement.”
Dr. Shields agreed. “Ocular ultrasound is really important with metastases because they tend to be echogenic, whereas melanoma tends to be echolucent. A fluorescein angiogram also is useful because metastases tend to be hypofluorescent in the early angiogram and later show diffuse patchy fluorescence with multifocal leaks in the RPE. It’s those leaks that lead to retinal detachment.” Optical coherence tomography, she added, will help determine if subretinal fluid is present and is a good way to follow these lesions. Fine-needle aspiration biopsy is reserved for patients who have a negative preliminary workup and is necessary for only 1 to 2 percent of her patients.
Treatment. Asymptomatic patients may simply be watched. If their systemic disease is out of control, these patients will be treated by their general oncologist. “But if the tumor is threatening vision, we’ll institute radiation therapy,” said Dr. Murray. “We use external beam radiation if there is multifocal involvement in one or both eyes. If there is only one tumor, the alternative is to do plaque radiotherapy."
Dr. Shields uses a plaque whenever possible because it takes only two days to complete, compared with daily radiation for four weeks with external beam radiation. This is especially important for patients who may have only a few months to live. Most patients treated with radiation maintain good vision.
Among patients with breast cancer metastases, Dr. Shields also is seeing good responses to hormonal therapy with the new aromatase inhibitors. In fact, she has had patients with complete ocular and systemic control on these agents. "The beauty of this treatment," she noted, "is that patients aren't sick, they can go about their daily activities and they are achieving systemic control."
For all patients with metastatic cancer, these and other quality-of-life issues assume major importance. "Our focus has been on preserving the eye and preserving function in the eye," Dr. Murray emphasized. "We don't want someone dying blind. It's critical to take good care of their eyes so that they have the best quality of life."
Colleague to Colleague
Treatment for ocular metastases requires a tight alliance between ocular and general oncologists. If a metastasis is the first indication of a systemic cancer—as it often is with lung cancer—the ocular oncologist may refer the patient to a general oncologist and advise the clinician about the type of tumor to look for. For patients with previously treated cancers, the ocular oncologist may begin the restaging process and, if necessary, treat the ocular metastasis while referring the patient back to the general oncologist.
The ocular oncologist also may play a role in monitoring the patient’s systemic therapy. “General oncologists love to have us see their patients because the eye is one of the few sites where you can actually see a metastasis and watch it respond to therapy,” noted Dr. Shields. “If a patient has a choroidal metastasis, we measure it and document it with photography. The general oncologist then gives the chemotherapy or hormone therapy and sends the patient back to us two months later and say, 'How are we doing?'”