Ординатура / Офтальмология / Английские материалы / Clinical Pathways in Glaucoma_Zimmerman, Kooner_2001

What Are the Presenting Signs and Symptoms?

Iris melanomas are usually slow-growing, well-defined lesions that may be pigmented or amelanotic. The diffuse type of iris melanoma is associated with unilateral acquired heterochromia and ipsilateral glaucoma. Thickening of the iris stroma with angle invasion may be seen gonioscopically. Spontaneous hyphema may also occur.3

Necrotic iris melanocytoma also causes secondary glaucoma and heterochromia. Differentiation of iris melanocytoma from iris melanoma may be difficult clinically and require histologic confirmation.7

Ciliary body melanomas appear as brown masses in the ciliary body. These tumors may grow circumferentially extending around the ciliary body (ring melanoma). Ciliary body melanomas may present with either angle-closure, open-angle, or neovascular glaucoma.

Choroidal melanoma is a variably pigmented mass that may be mushroomshaped and associated with retinal detachment. Angle closure may develop as the tumor enlarges; alternatively, rubeosis iridis and neovascular glaucoma may ensue.

Most commonly ocular metastases occur to the posterior pole as creamycolored lesions with an overlying (nonrhegmatogenous) serous retinal detachment. Intractable angle-closure glaucoma can develop with diffuse involvement of the posterior uvea. The anterior uvea is much less frequently involved with metastases, but has greater propensity to develop glaucoma either of the closedor open-angle forms. These anterior metastatic lesions appear as single or multinodular fleshy masses on the iris. They are friable, frequently seeding tumor cells into the angle, creating inflammation or pseudohypopyon. Rubeosis iridis is often associated. Ocular metastases may be the initial presentation of the malignancy. Shields et al31 report that 32% of patients have no history of a primary cancer when the diagnosis of iris metastasis was made. Frequent clinical findings in metastatic iris tumors include secondary glaucoma (38%), prominent epibulbar injection (40%), irregular pupil (60%), hyphema (15%), pseudohypopyon (10%), and choroidal metastasis (35%). The size of metastatic iris tumors ranged from 1 1 0.5 mm to 12 6 3 mm. The most common primary sites are breast and lung followed by gastrointestinal tract, kidney, thyroid, and skin.29,31,43,44

Retinoblastoma may present as leukocoria, strabismus, or glaucoma. The differential diagnosis of retinoblastoma is listed in Table 17–5. Classically, retinoblastoma occurs in infants or very young children. However, it may also occur in older children and adults. In one review of 400 consecutive cases of retinoblastoma, 8.5% of the patients were 5 years or older at the time of diagnosis.45 Clinically, retinoblastoma may initially present as acute orbital cellulitis. Although the presence of intraocular calcium is suggestive of retinoblastoma, the absence of calcium does not exclude this tumor. Diffuse infiltrating retinoblastomas may not exhibit calcification or distinct mass.46,47 Both endoand exophytic growth patterns may be associated with glaucoma that is usually seen only in the advanced stages of the tumor. Both angle-closure and neovascular glaucoma may develop.48,49

Medulloepithelioma of the iris or ciliary body appears as a solid or cystic grayish mass that is frequently associated with PAS and a shallow anterior chamber.

promise of the angle structures by forward displacement of the lens/iris diaphragm. Other authors confirmed this mechanism of angle closure in ciliary body melanoma.50 Friedman1 noted PAS most frequently secondary to rubeosis iridis, as an invariable association to angle-closure glaucoma. Neoplastic sources of rubeosis iridis were uveal melanoma, retinoblastoma, and metastatic cancer. Yanoff34 studied the histopathology of 19 eyes with melanoma and associated glaucoma. In the group with angle closure, PAS was a consistent finding, whereas iris bombé, posterior synchiae, rubeosis iridis, and diffuse iris melanoma were variably present. In the group with open-angle glaucoma, aqueous drainage was obstructed. This occurred from seeding of tumor cells into the anterior chamber, by invasion of angle structures (as in ring melanomas), or by melanin-laden macrophages blocking the angle (melanomalytic glaucoma). Shields and Proia51 described neovascular glaucoma occurring with isolated rubeosis iridis in iris melanoma without direct tumor involvement of the angle. A secondary glaucoma associated with spontaneous hyphema may also occur (Fig. 17–1).

IRIS MELANOMA

Iris melanoma most frequently directly invades the trabecular meshwork, but tumor seeding, melanin granules, or macrophage laden with melanin may obstruct the angle; secondary glaucoma from hyphema or rubeosis iridis has also been reported.33,35 A case report of iris ring melanoma associated with unilateral glaucoma and mistaken for unilateral pigmentary glaucoma cautions one in diagnosing atypical but increased angle pigmentation.36

CILIARY BODY MELANOMA

Ciliary body melanoma may cause angle-closure glaucoma by compressing the iris root into the angle or by forward displacement of the lens-iris diaphragm by the expanding mass creating a pupillary block.52 Iris bombé subsequently develops followed by formation of PAS and a secondary angle closure. PAS and angle closure may also develop as a result of rubeosis iridis. Alternatively, invasion of the angle by tumor or seeding of neoplastic cells or melanin granules from necrotic tumors may lead to mechanical obstruction of the trabeculum and open-angle glaucoma.2

CHOROIDAL MELANOMA

Choroidal melanoma is associated with glaucoma by iris and angle neovascularization, tumor necrosis-induced inflammation, pigment dispersion, or anterior displacement of the lens-iris diaphragm. This is a mass effect of the tumors with or without a retinal detachment or swelling of the lens.2,53

IRIS AND CILIARY BODY METASTASES

Metastatic tumors to the iris and/or ciliary body produce glaucoma by invading the angle structures or by covering them with sheets of tumor cells. Other mechanisms include pigmentary dispersion and hemolytic, uveitic, and neovascular forms of glaucoma.

CHOROIDAL METASTASES

In contrast, choroidal metastases affect IOP only with large mass size that is associated with choroidal or total retinal detachment. Subsequently, angle closure develops from displacement of the lens-iris diaphragm.2,44 The formation of PAS may also lead to angle closure.54

LEUKEMIA

Glaucoma may occur in leukemia by direct infiltration of angle structures, or be associated with hypopyon or hyphema.55 Massive subretinal or choroidal hemorrhage has reportedly been associated with cases of angle closure.2,4,56–58

LYMPHOMA

Intraocular lymphoma may directly infiltrate the uveal tract or be associated with a nongranulomatous uveitis causing a secondary IOP elevation.59

RETINOBLASTOMA

Many studies of retinoblastoma confirm that iris neovascularization is the most frequent cause of glaucoma.2 Angle closure from anterior displacement of the lens-iris diaphragm secondary to massive, exudative retinal detachment may occur. Less frequently, there is tumor seeding or shedding of necrotic tumor cells into the anterior chamber, uveitis, or hyphema.13,38

MEDULLOEPITHELIOMA

Histopathologic specimens of medulloepithelioma associated with glaucoma confirm the presence of rubeosis iridis, PAS, and shallow anterior chamber.18 Narrow-angle glaucoma may also be produced by the large mass effect posteriorly causing forward displacement of the lens-iris diaphragm. Direct infiltration of the angle by tumor cells or hyphema may cause a form of open-angle glaucoma.6,18

IRIS MELANOCYTOMA

Iris melanocytoma may be associated with glaucoma. Shedding of tumor cells or necrosis of the tumor with pigment dispersion into the anterior chamber compromises the trabecular meshwork.7,23,60 Rare reports of optic disc melanocytoma describe glaucoma resulting from the massive tumor size causing forward displacement of the lens-iris diaphragm and angle closure.22

JUVENILE XANTHOGRANULOMA

This tumor may be associated with either a vascular iris or ciliary body mass that produces glaucoma due to its hemorrhagic or inflammatory propensity. Open-angle glaucoma occurs from hyphema, uveitis, or even histiocytic invasion of the angle.18,61

418 Glaucoma Associated with Intraocular Tumors

diagnosed by clinical exam. Additionally, he cautions that an eye with opaque media and glaucoma not responding to conventional therapy must be suspect for undiagnosed melanoma. The ocular examination should include IOP measurements, biomicroscopy, gonioscopy, and dilated fundus exam. The exclusion of tumor associated with glaucoma or the risk of glaucoma with a known intraocular tumor needs to be assessed. All eyes with rubeosis iridis should undergo gonioscopy to exclude a mass lesion in the angle. The angle should be studied for patterns of pigmentation, configuration, depth, and evidence of previous inflammation such as PAS. The iris surface should be examined for rubeosis iridis, heterochromia, ectropion uveae, and mass lesions. Translucent, gelatinous nodules are typical of metastases; the hallmark of neurofibromatosis is the variably colored dome-shaped stromal iris elevations known as Lisch nodules. Variably pigmented iris lesions are present in melanoma and melanocytoma.

Stereo slit-lamp and fundus photographs are important for documentation and growth observation. B-scan ultrasound may aid in defining the solid or cystic nature of a lesion, the nodularity or dimensions, and the characteristic reflectivity. This technique may be used to exclude possible extension of an anterior chamber mass from the ciliary body. High-resolution (50 MHz) ultrasound biomicroscopy (UBM) has been used in eyes with impaired visualization of the anterior segment. Lanzl et al72 described the use of this technique in an eye with metastatic cancer, hypopyon, and elevated IOP. Excisional biopsy of an iris mass, by peripheral or sector iridectomy, with frozen sections may assist in the differentiation of iris nevus versus melanoma. Confirmation of melanin granules (from necrotic tumor) or tumor seeding into the anterior chamber can be obtained by aqueous aspiration and Papanicolaou stain. Two limbal nodules of extrascleral extension from a ring melanoma were biopsied by Allaire et al35 to confirm the diagnosis prior to enucleation. Fine-needle aspiration biopsy of iris ring melanoma was employed by Chaudhry et al36 and by others of ciliary body and choroidal melanoma for cytologic diagnosis. Additional tests to be considered are fluorescein angiography, computed tomography (CT), magnetic resonance imaging (MRI),53 and transillumination. The 32P test has been used as a diagnostic adjuvant in the differentiation of benign from malignant choroidal lesions. This test is based on the principle that malignant tumor cells incorporate and use phosphorus to a greater degree than do normal tissues.73 However, the 32P test is not frequently employed because other methods such as ultrasonography, fluorescein angiography, ophthalmoscopy, and fine-needle aspiration biopsy are more accurate. Various authors have encouraged a thorough evaluation of intraocular masses especially those associated with glaucoma and opaque media. Unnecessary surgery, risking tumor dissemination, should be avoided.53,73,74

RETINOBLASTOMA

The diagnosis of retinoblastoma is largely dependent on the clinical exam. Ultrasound, CT scan, MRI, and fluorescein angiography may be employed. Recently there has been little use of invasive techniques such as aqueous aspirates assessing lactic acid dehydrogenase levels to diagnose retinoblastoma.

Vitrectomy and fine-needle aspirates are also contraindicated due to the risk of tumor dissemination.48

MALIGNANT LYMPHOMA AND LEUKEMIA

These tumors are largely diagnosed in the context of the systemic disease. Transocular fine-needle aspirate or vitreous biopsy with cytology may be helpful.

MEDULLOEPITHELIOMA

En bloc resection (by iridectomy or iridocyclectomy) will ultimately provide histologic diagnosis if the tumor is well localized. However, the clinician may utilize indirect ophthalmoscopy and slit-lamp biomicroscopy to facilitate the diagnosis. Most eyes with medulloepithelioma have been diagnosed and treated by enucleation with or without exenteration.6,18,75

MELANOCYTOMA

Melanocytoma of the iris may be investigated through the techniques of transillumination (to exclude a cystic structure), ultrasonography (demonstrating the solid tumor with low internal reflectivity), fluorescein angiography (blocked fluoresence), high-frequency ultrasound biomicroscopy, fine-needle biopsy, or excisional biopsy.8 Slit-lamp examination and gonioscopy are paramount; heterochromia and tumor necrosis may be present. Release of pigment from the necrotic melanocytoma stimulates an intense macrophagic response that infiltrates the trabecular meshwork. Although fine-needle aspiration biopsy may facilitate the diagnosis of intraocular tumors, Fineman et al7 caution that fine-needle biopsy may not diagnose an occult focus of melanoma, and a negative cytologic diagnosis for malignancy does not rule out an intraocular malignancy. Therefore, they recommend local resection of an iris tumor as preferable to biopsy.

JUVENILE XANTHOGRANULOMA

Biopsy of other skin lesions demonstrating foamy histiocytes may assist in the diagnosis of juvenile xanthogranuloma of the iris.

NEUROFIBROMATOSIS

Neurofibromatosis and François syndrome may be further diagnosed by CT and general physical examination looking for evidence of gigantism, café-au-lait spots, or neurofibromas. Lisch nodules of the iris are noted on slit-lamp examination more than 90% of the time.76,77 Fluorescein angiography may further delineate the chorioretinal hamartomas; visual field testing, color vision evaluation, and CT or MRI may be useful in evaluating optic nerve gliomas. Ultimately in the evaluation of all tumors, enucleation with histologic staining and scanning electronmicroscopy may be employed for definitive diagnosis (Fig. 17–1).