Intraocular Metastasis Onset

Ocular metastases from any primary site typically occur in the sixth to seventh decade of life at a mean age at 58 years (median 58 years, range 10–85 years) [2]. For breast cancer metastasis, the mean age at diagnosis of the ocular metastasis was 56 years (median 57 years, range 23 years to 84 years) [17].

Most patients with ocular metastases from breast cancer have a known history of breast cancer and previous nonocular metastases. Of 264 patients with uveal metastasis from breast cancer, the eye finding was the first manifestation of breast cancer in 3% [17]. In 14% of patients, the ocular metastasis was the first metastatic site. The locations of systemic nonocular metastases prior to and following the detection of ocular metastasis are listed in Table 14.2.

Of those patients who develop ocular metastases, the mean age at diagnosis of the primary breast cancer was 56 years (median 57 years, range 23–84 years) [17]. The initial treatment of breast cancer was radical or modified mastectomy (83%), systemic chemotherapy (42%), external beam radiotherapy (27%), lumpectomy with or without lymph node dissection (14%), and hormone therapy (4%). The axillary lymph nodes were involved in 46% of patients who developed eventual uveal metastases. At the time of diagnosis of the ocular metastases, 52% of patients were on systemic therapy, including chemotherapeutic agents (36%), hormone therapy (20%), and immunotherapeutic agents (2%). Uveal metastases developed a mean of 65 months following the diagnosis of the primary breast cancer (median 48 months, range 0–300 months) [17].

Location and Multiplicity

of Intraocular Metastasis

Intraocular metastases show a strong tendency to involve the posterior uvea (choroid). Less commonly, the tumor affects the iris or ciliary body. Rarely do metastases involve the optic disk or retina. Of 361 eyes with uveal metastases, the

Table 14.2 Locations of systemic nonocular metastasis before and after the uveal metastasis was established in 264 consecutive patients with uveal metastasis from breast cancer [17]

tumor was located in the choroid in 349 eyes, iris in 23 eyes, and ciliary body in 2 eyes (see Fig. 14.1) [17]. Some patients had metastatic tumors in more than one intraocular location.

In general, intraocular metastases commonly show multifocality and/or bilaterality. In an analysis of 520 eyes with uveal metastases from all primary sites, the median number of metastatic tumors per eye was 1 and the mean was 1.6 [2]. Furthermore, 370 (71%) eyes had 1 focus, 63 (12%) had 2 foci, 87 (17%) had 3 or more foci, up to a maximum number of 13 metastatic foci in one eye [2]. The tumor was unilateral in 76% and bilateral in 24% of patients. With regard to ocular metastases from breast

cancer, the tumor was unilateral in 62% and bilateral in 38% [17]. Of 99 patients (38%) with bilateral uveal metastases from breast cancer, 85 (32%) had bilateral involvement at the time of diagnosis and 14 (5%) developed the second eye involvement after a mean follow-up of 10 months (median 7 months, range 2–33 months). The mean number of the uveal metastatic tumors (from breast cancer) per eye was two (median 1, range 1–19) and more than one metastatic focus was detected in 48% [17].

Clinical Features of Intraocular

Metastasis

Choroidal Metastases

The patient with a metastatic tumor to the choroid may be asymptomatic or may experience

painless blurred vision. In rare instances, pain caused by secondary glaucoma can be the initial manifestation. Ophthalmoscopic examination of a choroidal metastasis characteristically reveals a homogeneous, creamy yellow placoid lesion in the posterior choroid (Fig. 14.4) [2, 27, 28, 33]. Tumors that are slightly more elevated can produce a serous detachment of the retina and alterations in the retinal pigment epithelium (RPE). The RPE changes can be marked, appearing as well-delineated clumps of golden brown pigment on the surface of the tumor. In some instances, the tumor may appear multinodular.

In some cases, a choroidal metastasis can be highly elevated and have a dome shape, similar to a primary amelanotic melanoma [34]. The finding of multiple choroidal tumors in such a case, however, is strong evidence for a metastatic tumor rather than a primary melanoma, which is usually solitary (Figs. 14.5 and 14.6).

Serous detachment of the sensory retina is associated with choroidal metastases from breast cancer in 64% of cases [17]. In some instances, the detachment only involves the fovea adjacent to the tumor, whereas in other cases, it may be bullous. When the detachment is extensive, dramatic shifting of the subretinal fluid can be demonstrated with movements of the patient’s head.

Several conditions can clinically simulate a metastatic cancer to the choroid and should be considered in the differential diagnosis [35]. These include amelanotic nevus, amelanotic melanoma, hemangioma, osteoma, posterior scleritis, retinitis and choroiditis, rhegmatogenous retinal

detachment, Harada’s disease, uveal effusion syndrome, and central serous chorioretinopathy [27, 28, 35–37]. A detailed history is often helpful in making the differentiation, but the ophthalmoscopic differences are also very important. The specific clinical features of the various tumors and pseudotumors are illustrated in textbooks [27, 28]. With some experience, the clinician can differentiate simulating lesions from metastatic tumors by their typical ophthalmoscopic features and by using ancillary diagnostic procedures, to be discussed subsequently.

A choroidal melanoma is the most important lesion to differentiate from a metastatic tumor [34]. The melanoma is characteristically

pigmented but can be completely amelanotic and closely resemble the color of a metastasis. The melanoma is typically unilateral, solitary, and more elevated. An amelanotic melanoma frequently has large visible intrinsic blood vessels and often assumes a mushroom shape from herniation through Bruch’s membrane; these findings rarely occur with a metastatic tumor.

A choroidal hemangioma can also resemble a metastatic tumor in size, shape, and location [36]. The distinct red-orange color of most hemangiomas differentiates them from the yellow color of a metastatic tumor. A choroidal hemangioma is classically unilateral and unifocal.

Achoroidal osteoma characteristically appears as an amelanotic choroidal mass [37]. Like a metastatic tumor, it is more common in women. In contrast to a metastatic tumor, it has an irregular but well-defined border and can show subretinal neovascularization on the surface. We have seen one patient who underwent three breast biopsies elsewhere because a choroidal osteoma was suspected to be a metastatic cancer before the correct diagnosis was eventually established. Ultrasonography and computed tomography of a choroidal osteoma reveal echoes characteristic of a calcified plaque.

A number of inflammatory processes of the fundus can simulate a choroidal metastasis. Certain viral and mycotic infections are more commonly seen in patients with systemic cancer, thus making the differentiation even more difficult. Patients with cytomegalovirus (CMV) retinitis often have a history of cancer and are on chemotherapy. The yellow-white areas of retinal necrosis may be bilateral and multiple. In contrast to metastatic tumors, they involve the retina rather than the choroid, have an irregular border, and frequently show surrounding and overlying retinal hemorrhages. Mycotic retinitis or choroiditis also can resemble a choroidal metastasis, but it is more likely to be associated with inflammatory signs.

Ciliary Body Metastases

Ciliary body metastases are often difficult to detect clinically. They can masquerade as a chronic uveitis or secondary glaucoma, and the

affected patient may be treated with topical or systemic corticosteroids or glaucoma medications, while the tumor remains undetected. Like primary ciliary body melanoma, a ciliary body metastasis can produce a shallow anterior chamber, subluxated lens, or cataract. Prominent episcleral blood vessels can occur in the quadrant of the lesion. In some cases, the ciliary body may be involved because of anterior extension of a diffuse tumor from the choroid. With time, some ciliary body metastases can extend through the iris root into the anterior chamber. The differential diagnosis of a ciliary body metastasis includes many of the same conditions that fall under the differential diagnosis of choroidal metastasis, except for those that affect only the posterior pole, such as central serous chorioretinopathy, choroidal hemangioma, and osteoma.

Iris Metastases

The clinical presentation of iris metastases can be vary greatly [2, 29]. Some patients with iris metastases are visually asymptomatic or with only mild symptoms. In some instances, however, pain caused by inflammation or secondary glaucoma can be the presenting manifestation in some instances. Occasionally, iris metastases are multiple and bilateral. Slit lamp biomicroscopy reveals an iris mass that is usually pink or white, depending on the intrinsic vascularity (Fig. 14.7). In some cases, iris metastases are friable, and loosely cohesive cells settle in the inferior portion of the anterior chamber angle, producing a pseudohypopyon, simulating endophthalmitis. The differential diagnosis of metastatic tumors to the iris includes amelanotic melanoma, leiomyoma, granulomatous iritis, and endophthalmitis.

Retinal Metastases

Metastatic tumors to the retina are extremely rare. In contrast to choroidal metastases, retinal metastases are less cohesive and may seed tumor cells into the vitreous. They sometimes resemble a retinitis and can have associated exudation or hemorrhage (Fig. 14.8).