Multiple intraocular tumors are associated with glaucoma or ocular hypertension. Although these cases are relatively rare, glaucoma secondary to an intraocular tumor is a critical diagnosis that should not be missed, because the lesion may represent a life-threatening malignancy. Clinicians should maintain an appropriate degree of suspicion for an underlying tumor in patients who present with atypical glaucoma. The differential diagnosis for any unilateral or markedly asymmetric glaucoma should include an underlying malignancy. Other clinical features possibly suggesting an intraocular tumor include iris heterochromia, a lack of response to IOP-lowering treatment, persistent uveitis that is unresponsive to steroids, unilateral pigment dispersion, serous retinal detachment with elevated IOP, and dilated episcleral vessels.1

The mechanism by which intraocular tumors raise IOP is variable and depends on many characteristics, including the tumor's type, location, size, and duration. The most commonly described mechanism is tumor invasion or seeding of an open anterior chamber angle in addition to a secondary pigment dispersion syndrome.2 Angle closure may also occur from a large compressive lesion, associated choroidal detachment or hemorrhage, or neovascularization of the iris and/or angle.1

UVEAL MELANOMAS

Uveal melanomas are the most common primary intraocular malignancy and are frequently implicated as a secondary cause of glaucoma (Figure). According to the literature, the prevalence of elevated IOP in eyes with uveal melanoma ranges from 3% to 57%, with the largest and most recent series by Shields et al reporting elevated IOP in only 3% of eyes.2,3

The location of the melanoma is important when determining the risk of secondary glaucoma. Ciliary body melanomas present the greatest risk, followed by iris and then choroidal locations. Choroidal melanomas most commonly elevate IOP via neovascularization of the iris and synechial angle closure. Large posterior tumors with subsequent total retinal detachment or massive choroidal hemorrhage may also result in acute angle closure by anterior displacement of the lens-iris diaphragm. Iris melanomas are often easily identified on slit-lamp examination or gonioscopy as a hyper- or hypopigmented stromal mass, which may have associated sentinel vessels. Most often, they raise IOP through direct invasion of the angle. Ciliary body melanomas are often difficult to detect and can masquerade as uveitis or a ciliary body cyst. These tumors may also invade the angle, resulting in increased IOP. Alternatively, they may cause a unilateral pigment dispersion syndrome. Any type of intraocular melanoma may result in a melanomalytic glaucoma, described as an obstruction of the anterior chamber angle by melanin-laden macrophages.1

SYSTEMIC MALIGNANCY

Ocular metastases of systemic malignancies may result in secondary glaucoma. The most common site of metastasis is the choroid, whereas glaucoma is much more likely found with anterior segment metastases.1 In general, the published rates of glaucoma in ocular metastasis range between 5% and 7.5% but increase to 56% to 67% when the metastasis is located in the anterior segment.2,4,5 Tumor invasion of the anterior chamber angle is the most common mechanism in these eyes, with malignant cells often lining or infiltrating normal trabecular meshwork to obstruct aqueous outflow. The most common primary sites for tumors are the lung and breast, but they may also result from cutaneous melanomas and gastrointestinal cancers, among others.1

Children and adults with leukemia may present with elevated IOP as a result of leukemic infiltration of the anterior segment. Although the rate of glaucoma in these patients is unknown, autopsy studies have shown that 28% of patients with acute or chronic leukemia had ocular leukemic infiltrates.6 Manifestations on examination may include iritis, hypopyon, and/or hyphema. As malignant, inflammatory, and red blood cells move into the anterior chamber, the trabecular meshwork and Schlemm canal become obstructed, resulting in an increase in IOP. Posterior involvement can lead to acute angle closure in some patients. Acute lymphocytic leukemia is the most common source of intraocular spread as well as of secondary glaucoma.1 Multiple myeloma, lymphoma, and metastatic melanoma are among other systemic malignancies capable of producing a secondary glaucoma.

CHILDHOOD TUMORS

Retinoblastoma should be considered in the differential diagnosis of any pediatric glaucoma or uveitis. Glaucoma can be the presenting clinical sign in up to 7% of patients, with histologic evidence of a glaucomainducing mechanism found in 50% of eyes.1,7 Clinically, elevated IOP can occur in 17% to 23% of retinoblastoma cases, with much larger, advanced tumors conferring a much higher risk of elevated IOP.1 Neovascularization of the anterior segment is the most common mechanism, followed by angle closure from a large, compressive lesion and tumor infiltration of the angle.2

DIAGNOSIS AND WORKUP

The workup of patients with atypical glaucoma and a suspected intraocular tumor starts with a complete ocular and medical history focusing on risk factors for cancer. In contrast to primary glaucoma, these patients often possess one or more ocular symptoms. A slit-lamp examination of the anterior chamber may reveal suspicious signs of a tumor, including dilated episcleral sentinel vessels, pigment dispersion, iritis, hypopyon, or hyphema. Clinicians should perform gonioscopy to look for a mass lesion in the angle, neovascularization, an abnormal iris configuration, or angle closure. A full, dilated fundus examination allows assessment of the posterior segment for evidence of a tumor. If the posterior view is obstructed, B-scan ultrasonography may be helpful. Ultrasound biomicroscopy is useful for detecting and differentiating posterior iris and ciliary body lesions as well as for illustrating potential mechanisms for IOP elevation.

If the practitioner's suspicion of a tumor is high, but the diagnosis is uncertain, he or she may use more invasive diagnostic techniques such as a fine-needle aspiration biopsy with a vitrectomy or a small-incision iridectomy. If lymphoma or leukemia is suspected, a paracentesis of the anterior chamber may be performed. A metastatic workup is indicated in all tumor diagnoses, which may include any combination of a computed tomography scan, magnetic resonance imaging scan, or positron emission tomography-computed tomography scans in addition to laboratory studies. An ocular tumor specialist and/or oncologist should be involved as soon as possible to direct the treatment of the underlying tumor.

MANAGEMENT

The management of glaucoma associated with intraocular tumors is generally centered on the treatment of the underlying malignancy. This may include surgical resection, radiation, and chemotherapy. It is important to note that secondary glaucoma may arise as a result of these treatments, even if it is not present beforehand. Incisional glaucoma surgery is contraindicated in eyes with primary intraocular tumors due to the potential risk of metastasis. Therefore, topical and oral hypotensive medications should be used primarily to reduce the IOP, followed by cyclophotocoagulation. Laser iridotomy may be considered to relieve pupillary block, but it may not be successful and should be avoided when a tumor involves the iris.1 Because the visual prognosis is often poor in eyes with secondary glaucoma, enucleation may be indicated as initial treatment or in refractory cases.

Leonard K. Seibold, MD, is an assistant professor of ophthalmology at the University of Colorado Eye Center in Denver. Dr. Seibold may be reached at leonard.seibold@ucdenver.edu.

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