Chapter 16

Uveal Metastases from Solid Tumors

Gerardo D. Camoriano and Dan S. Gombos

Abstract Because the uveal tract is a highly vascular structure with a low-flow microenvironment, it is well suited for seeding of circulating cancer cells. Numerous studies have shown that uveal metastases are the most common intraocular malignancies in adults. The most common primary cancers metastasizing to the uvea are breast and lung cancers. The most common symptom of uveal metastasis is blurred vision; however, patients may also present with vision loss, intraocular pain, scotoma, floaters, photopsias, and metamorphopsia. Treatment modalities include observation, external-beam radiation therapy, chemotherapy, plaque brachytherapy, transpupillary thermotherapy, and enucleation. For many patients, uveal metastasis is associated with advanced systemic disease, which portends a poor prognosis; however, early diagnosis and treatment of uveal metastasis can result in good visual outcomes and high rates of ocular salvage.

16.1 Introduction

Cancer is the second most common cause of death in the United States, contributing to nearly one in four deaths. As the incidence rate of cancer increases, it is likely that an ophthalmologist in general practice will encounter a patient with ocular metastasis.

Numerous studies in the past 10 years have shown that uveal metastases are the most common intraocular malignancies in adults. Given that the uveal tract is a highly vascular structure with a low-flow microenvironment, it is not surprising that the uveal tract is well suited for seeding of circulating cancer cells. Cases of ocular metastases outnumber cases of primary uveal melanoma by a ratio of approximately 2:1 [1–3]. Within the uvea, the most common site of involvement is the choroid,

G.D. Camoriano (B)

Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch, Galveston, TX, USA

e-mail: gdcamori@utmb.edu

Oncology Series 6, DOI 10.1007/978-1-4419-0374-7_16,

C Springer Science+Business Media, LLC 2011

which has a comparatively large surface area and distribution of blood flow. In some cases, metastatic disease goes clinically unrecognized during the patient’s lifetime and is only identified when the eye is examined at autopsy. In most patients, however, uveal metastasis presents with painless blurred vision, which, in the context of a previous history of systemic malignancy, mandates an urgent ocular assessment. Hence, the ophthalmologist may be the first physician to discover the recurrence of a previously treated cancer or detect a previously unknown primary cancer in a patient without any history of cancer.

16.2 Patient Characteristics

Uveal metastases have been reported in patients in every decade of life. Women (70–85% of cases) are more commonly affected than men. Lung and breast adenocarcinomas account for the majority of uveal metastases, with estimates ranging from 71 to 92% of cases. Incidences of uveal metastatic tumors parallel those of the corresponding primary tumors. In men with uveal metastases, the most common primary cancer site is the lung (40–60% of cases), while in women with uveal metastases, the most common primary cancer site is the breast (70–80% of cases), followed by the lung (10% of cases) [4–6]. It should be noted that uveal metastases related to primary breast cancer have also been reported in men and that lung cancerassociated uveal metastases are expected to become more common in women as the incidence of primary lung cancer in women continues to increase. Other adenocarcinomas that metastasize to the eye include gastrointestinal, prostate, kidney, and thyroid adenocarcinomas [7]. Germinal tumors from the ovaries and testes and cutaneous melanoma have also been shown to metastasize to the uvea. Although rare, metastasis from neuroendocrine tumors, particularly carcinoid tumors, has also been known to occur [8].

16.3 Symptoms

Symptoms of ocular metastases depend on the location of the tumor. Tumors affecting the posterior pole often present earlier, and visual complaints are common, particularly when the macula is involved. The most common initial symptom is blurred vision, which may result from exudative retinal detachment or subretinal fluid or from a hyperopic shift secondary to mass effect. Similarly, iris or ciliary body metastases may result in displacement of the lens diaphragm, causing new refractive errors. Alternatively, vision loss may be caused by an iritis or iridocyclitislike inflammation due to tumor seeding in the anterior chamber. Extensive seeding in the anterior segment may also result in the formation of a pseudohypopyon. Visual acuity can range from 20/20 to no light perception; visual acuity is commonly severely affected at presentation [4, 5].

Intraocular pain is not common but may be present in up to 16% of patients who have ocular metastases. This is generally a dull, boring, and constant pain; however, it may be sharp and intermittent. Secondary angle closure from tumor debris,

neovascular glaucoma from anterior segment ischemia, and perineural invasion of the ciliary nerves may also lead to intraocular pain. Other symptoms of ocular metastases include scotoma (6–31% of patients), floaters (5–21% of patients), photopsias (13% of patients), and metamorphopsia (3–5% of patients).

16.4 Clinical Features

All patients with a history of cancer should have a thorough annual ophthalmic examination. The iris should be carefully inspected with a slit lamp for the presence of nodules. Most iris metastases occur in the inferior quadrant (42% of cases), and iris metastases are more likely to affect the midzone than the pupillary margin or iris root. Ciliary body metastases are usually sessile or dome shaped. They are often difficult to visualize directly but should be suspected when there is segmental distortion of the pupil or lens diaphragm. If not apparent on slit lamp or ophthalmoscopy, ciliary body metastases can often be seen with gonioscopy or high-frequency ultrasound biomicroscopy. Ciliary body metastases, like their iris counterparts, often occur in the inferior quadrant (48% of cases). Other clinical signs associated with iris or ciliary body metastases include conjunctival hyperemia, glaucoma, corectopia, iridocyclitis, pseudohypopyon, and hyphema.

A dilated fundus examination should be performed to identify choroidal lesions, since the choroid is the most common site for metastasis to the uvea. Choroidal lesions are most commonly seen in the near periphery (52–83% of cases), followed by the macula (up to 40% of cases) and mid and far periphery (together accounting for 8–17% of cases). Radially, the lateral quadrant (35% of cases) is affected slightly more often than the superior (22% of cases), inferior (17% of cases), nasal (14% of cases), and central (macula) quadrants (12% of cases). Choroidal tumors are usually cream-colored or pale yellow and placoid or slightly dome shaped, with oval or irregular margins. They may be associated with subretinal fluid and shallow exudative retinal detachments.

Uveal metastases of bronchial carcinoids, renal cell carcinoma, and thyroid cancer may be orange, and cutaneous melanomas are brown. Overlying lipofuscin deposits may confer a leopard skin appearance. Careful examination reveals the presence of multifocal disease in 29–35% of cases and bilateral eye involvement in up to 50% of patients.

16.5 Diagnosis

In the diagnosis of uveal metastases, the importance of obtaining a patient’s complete medical history cannot be overemphasized. Particular attention should be given to the patient’s chief complaint and past medical history, which often narrows the differential diagnosis.

Ancillary techniques, such as gonioscopy and high-frequency ultrasound biomicroscopy, may be necessary to evaluate lesions involving the iris root or ciliary body. Traditional A- and B-scan ocular echographic images are helpful in assessing most