Melissa G. Tong,
Randall R. Ozment,
Teresa C. Chen
GENERAL CONSIDERATIONS - OVERVIEW
The number of patients with glaucoma associated with intraocular tumors is small. Nevertheless, because of the morbidity and mortality associated with many ocular tumors, proper diagnosis and treatment of the tumor and its related complications (e.g., glaucoma) is important for the well-being of the patient. The systemic well-being of the patient must always be considered paramount in caring for patients with ocular tumors. The treatment of tumor-related glaucoma is of secondary importance to the treatment of the tumor itself. This is particularly true when the tumor is malignant and potentially fatal.
There are many mechanisms by which ocular tumors can cause glaucoma (Table 209.1). This results in a wide gamut of clinical presentations of glaucoma associated with ocular tumors. Some mechanisms are common to other glaucomas and are familiar to clinicians. Examples are pigment dispersion and neovascularization of the anterior segment. Other mechanisms are rare and are related to specific tumor types. These mechanisms are discussed with each tumor type when appropriate.
TABLE 209.1 -- Mechanisms of Glaucoma Due to Ocular Tumors
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Open Angle |
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Pigment dispersion |
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Melanomalytic (pigment-laden macrophages obstructing outflow) |
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Inflammatory (necrotic tumor inducing inflammation) |
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Tumor cells seeding trabecular meshwork |
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Direct growth of tumor into trabecular meshwork |
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Hemorrhagic glaucoma (secondary to recurrent intracameral hemorrhage from tumor) |
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Angle Closure |
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Mechanical angle closure due to anterior displacement of lens-iris diaphragm by posterior tumor mass effect |
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Neovascular glaucoma |
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Suprachoroidal hemorrhage due to tumor with anterior displacement of lens-ris diaphragm |
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Tumor cell-induced peripheral anterior synechiae |
GENERAL PRINCIPLES OF DIAGNOSIS AND MANAGEMENT
Several articles[1-4] on ultrasound biomicroscopy in the management of various ocular tumors have noted its usefulness, particularly in cases where conventional B-scan ultrasonography did not make the diagnosis.[3,4]
Management of ocular tumors often requires enucleation of the eye to limit morbidity and mortality. In these patients, the management of glaucoma is not an issue. However, in eyes that retain good vision and do not require enucleation, management of the tumor-related glaucoma may be necessary.
Medical management of glaucoma may be effective in many eyes with ocular tumors. In other cases, surgical therapy may be needed. Laser treatment is controversial, due to the possibility of intraocular spread of tumor cells and the low success of achieving intraocular pressure (IOP) control.[5] In general, eyes with malignant tumors should not undergo fistulizing operations for the control of eye pressure. These procedures may also result in extraocular spread of malignant tumor cells. Filtering surgery may be appropriate for eyes with benign tumors. Depending on the location of the tumor, it is theoretically possible that tube shunt surgery may induce a lower risk of extraocular tumor spread.
A study on 237 patients with large uveal melanomas found that patients treated by transscleral tumor resection obtained better results in terms of visual function and had lower incidences of secondary glaucoma than patients treated with 125I plaque brachytherapy.[6] However, a later study of iodine brachytherapy in 96 uveal melanoma patients found that IOP at diagnosis and preoperative exudative retinal detachment were associated with time to glaucoma.[7]
HISTORICAL CONSIDERATIONS
The association of intraocular tumors and glaucoma has long been recognized. von Graefe has been credited with the dictum, 'the degree of tension of the eyeball is a guide to diagnosis'.[8] In years past, great emphasis was given to the presence or absence of glaucoma in order to differentiate between rhegmatogenous retinal detachment and tumor-related retinal detachment. In 1896, Marshall reported his findings of associated glaucoma and intraocular tumors from his study of 100 eyes enucleated for 'malignant disease both of the choroid and also the retina'.[9] His study included uveal melanoma and retinoblastoma. Marshall found elevated IOP in 53% of the eyes he studied. He also reported decreased IOP in 7% and normal IOP in 40%. In his attempt to understand the mechanism of glaucoma secondary to intraocular tumors, Marshall reported a close correlation of the width of the anterior chamber angle to the development of glaucoma. Most eyes with glaucoma were found to have a closed angle or 'restricted angle'. Marshall states: 'in all cases tension bears a direct relation to the size and condition of the angle of the anterior chamber'.[9] He found a higher incidence of closed angles with tumors of the choroid than with those of the ciliary body.
In 1935, Terry and Johns reported a 33% incidence of glaucoma in eyes with uveal sarcoma.[10] Of 94 eyes, 23 were found histopathologically to have damage to the filtration angle as a result of a tumor being present within the eye.
Shields and co-workers presented the results of a survey of 2704 eyes with intraocular tumors.[11] One hundred twenty-six eyes, or 5%, were found to have a tumor-induced elevation of IOP. The survey included uveal melanoma, retinoblastoma, metastatic tumors, and other miscellaneous neoplasms. In their survey, metastatic tumors to the iris and ciliary body were more likely to result in elevated IOP than were choroidal melanoma and retinoblastoma.
To facilitate the ease of use of this chapter for the clinician caring for patients with intraocular tumors or glaucoma, it is divided into primary ocular tumors, metastatic tumors, and miscellaneous tumors with ocular involvement. Within the first two sections (primary ocular tumors and metastatic tumors), there is an anatomic division of the eye starting with the iris and then moving posteriorly to the ciliary body, optic nerve, retina, and finally the choroid. Specific tumors and secondary glaucomas are discussed under each anatomic subheading.
PRIMARY OCULAR TUMORS AND GLAUCOMA
PRIMARY IRIS TUMORS
Glaucoma secondary to iris tumors may occur with both benign and malignant neoplasms. Depending on the underlying mechanism producing the elevation of IOP, the clinical presentation of glaucoma secondary to iris tumors may be acute or chronic angle-closure glaucoma, chronic open-angle glaucoma, hemorrhagic glaucoma, or inflammatory glaucoma. The underlying mechanism of glaucoma may be direct invasion of aqueous outflow pathways by tumor cells; dispersion of pigment or melanin granules, causing obstruction of aqueous outflow pathways; tumor cell dispersion into the trabecular meshwork, causing obstruction of outflow; and inflammatory cells obstructing aqueous outflow.
Iris Nevus
Benign iris nevi are common clinical findings in many patients. Histologically, they consist of benign spindle-shaped cells. An iris nevus rarely results in a pathologic process in the eye. However, diffuse growth of an iris nevus within the anterior chamber and into the chamber angle involving the trabecular meshwork has been documented clinically and histopathologically.[12] A secondary open-angle glaucoma may result when a nevus grows to involve the angle and aqueous outflow pathways.
Iris Melanocytoma
This is a pigmented iris tumor composed of benign polyhedral nevus cells. It is a rare clinical entity. Pigment dispersion and secondary elevation of IOP with significant reduction of outflow facility has been documented in three eyes containing a necrotic iris melanocytoma.[1,13] In one case, after removal of the tumor by iridocyclectomy, the IOP and outflow facility returned to normal. This occurred concurrently with resolution of heavy pigmentation of the trabecular meshwork. Twenty-two years after iridocyclectomy, the IOP remains normal without medication.[14] The obstruction of outflow was thought to be secondary to pigment, and pigment and debris-laden macrophages collecting in the outflow pathways as it was released from the necrotic tumor.[14] A successful case of pupil sparing partial iridectomy has also been documented, without reformation of the tumor or recurrence of glaucoma after 3 years follow-up.[15] Direct involvement of the outflow pathways by an iris melanocytoma has also occurred, resulting in increased IOP with impaired facility of outflow.[16]
Iris Pigment Epithelium Adenoma
This is a rare benign tumor of the iris pigment epithelium. Glaucoma associated with this tumor has been attributed to pigment dispersion into the trabecular meshwork.[17] Resolution of the elevated IOP occurred after removal of the tumor by iridocyclectomy in a single case.
Iris Malignant Melanoma
Malignant melanoma of the iris may result in secondary tumor-induced glaucoma. The incidence of glaucoma associated with iris melanoma ranges from 7% to 48%.[11,18,19] Diffuse iris melanomas are more likely to result in secondary glaucoma than are smaller circumscribed tumors.[11]
Secondary glaucoma associated with primary iris melanoma may occur from several different mechanisms. Direct growth of solid tumor into the anterior chamber angle and aqueous outflow pathways, causing obstruction of aqueous outflow, is the most common mechanism of glaucoma associated with iris melanoma.[11,19] Both indirect seeding of aqueous outflow pathways by tumor cells and dispersion of pigment from iris melanomas have resulted in secondary open-angle glaucomas (Fig. 209.1).[11,18]
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FIGURE 209.1 Midstromal iris melanoma with extensive tumor seeding into the angle structures. |
Melanomalytic glaucoma is seen only in eyes with pigmented intraocular tumors and therefore may occur in eyes with iris melanoma.[20-22] Melanomalytic glaucoma results from an obstruction of aqueous outflow pathways by macrophages containing melanin granules dispersed from the tumor. Melanin-filled macrophages may occupy the anterior chamber angle and mechanically obstruct aqueous outflow. Light and electron microscopy of eyes with melanomalytic glaucoma has shown the trabecular meshwork surface and intertrabecular spaces filled with melanin-laden macrophages.[21]
The differential diagnosis of glaucoma secondary to iris tumors is relatively brief. Pigmentary glaucoma, uveitic glaucoma, glaucoma secondary to metastatic tumors to the iris, and variants of the iridocorneal endothelial syndromes may be confused with glaucoma secondary to primary iris tumors. However, with a tumor present on the iris, proper diagnosis is usually made clinically. In some patients, a fine-needle biopsy, aqueous aspiration, or excisional biopsy is needed to confirm the diagnosis.
Management of iris tumors in eyes with good visual acuity generally involves frequent observation of the lesion. Photographic documentation of the lesion is helpful in determining the stability or growth of the tumor. Most malignant iris tumors have relatively benign histopathologic characteristics and may be observed over long periods when the lesion is documented to be stable and nongrowing.[18,19,23]
Elevated IOP in eyes with iris tumors may be managed by medical means. Surgical fistulizing operations performed in eyes with malignant iris tumors carry the significant risk of promoting extraocular spread of tumor cells and are contraindicated.
Iris tumors of limited size may be removed by iridectomy or iridocyclectomy.[23] Eyes with tumors that result in pigmentary dispersion and glaucoma have had resolution of the pigment dispersion and glaucoma after removal of the tumor by iridectomy and iridocyclectomy.[11,17] Uncontrollable glaucoma secondary to iris tumors may require enucleation of the eye. For nonresectable tumors, plaque radiation is a reasonable alternative, with continuing medical therapy.[24] Proton beam radiotherapy was also studied in 88 patients, but the study found glaucoma difficult to control using this treatment.[25]
PRIMARY CILIARY BODY TUMORS
Benign and malignant tumors involving the ciliary body may result in increased IOP and glaucoma. However, many eyes with tumors of the ciliary body may have decreased IOP.[8,9,26,27] Hypotony may occur secondary to decreased aqueous production as a result of a tumor involving the ciliary body and ciliary processes. In many patients, only a mild relative hypotony is present when comparing involved and uninvolved eyes. Eyes with glaucoma secondary to ciliary body tumors have tumor-related pathology affecting the outflow pathways to a greater extent than the tumor pathology affecting aqueous production by involvement of the ciliary processes.
As with glaucoma related to iris tumors, the presentation of glaucoma related to ciliary body tumors may be varied. The glaucoma may present as acute or chronic angle-closure glaucoma, chronic open-angle glaucoma, hemorrhagic glaucoma, or uveitic glaucoma.[22,26,28] The presentation depends on the underlying mechanism producing the glaucoma (Fig. 209.2).
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FIGURE 209.2 Heterochromia caused by iris involvement of a ciliary body melanoma. Glaucoma was present in the left affected eye, whose iris appears darker in color. |
Ciliary Body Medulloepithelioma
Medulloepithelioma is a tumor that arises most commonly from the nonpigmented ciliary epithelium. There have only been three cases of pigmented medulloepitheliomas reported in the literature.[29] There may be a benign or malignant histopathologic appearance and clinical course. Medulloepithelioma generally occurs during childhood but may be seen in early adulthood.
In a large series of medulloepitheliomas involving the ciliary body, ~50% of the eyes had glaucoma at the time of initial examination.[28] Rubeosis iridis with resultant angle closure was a common cause of glaucoma associated with medulloepithelioma of the ciliary body. Direct tumor growth into the chamber angle involving outflow pathways was also documented. Tumor-induced angle-closure glaucoma caused by mechanical displacement of the angle structures also resulted in glaucoma in several eyes reported. A single eye acquired elevated IOP after recurrent intracameral hemorrhage and hyphema.[28]A single case of angle-closure glaucoma in an eye with meduloepithelioma due to peripheral anterior synechiae caused by disseminated tumor cells has been documented.[30]
Ciliary Body Melanocytoma
Melanocytoma, a benign pigmented tumor of the uveal tract, may occur in the ciliary body. Melanocytoma of the ciliary body has been associated with glaucoma. A single case report has demonstrated invasion of a ciliary body melanocytoma into the angle structures, resulting in elevated IOP and glaucoma.[31] This tumor may also undergo necrosis, resulting in glaucoma secondary to pigment dispersion.[32]
Ciliary Body Malignant Melanoma
As many as 17-55% of eyes with ciliary body melanoma may have a tumor-induced glaucoma.[11,26,27] Secondary elevation of IOP in eyes with ciliary body melanoma may be produced by a variety of mechanisms. Most commonly, pigment dispersion or direct invasion of the angle structures is found. In one large series of 96 eyes with ciliary body melanoma, pigment dispersion was the mechanism of pressure elevation in half the glaucomatous eyes.[33] Thirty-one percent of eyes with elevated IOP were found to have a direct tumor involvement of the angle structures by tumor growth from the ciliary body. Seeding of angle structures by tumor cells (Fig. 209.3), rubeosis iridis with neovascular glaucoma, and mechanical tumor-induced angle closure have all been reported as mechanisms of elevation of IOP in eyes containing ciliary body melanomas.
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FIGURE 209.3 Scanning electron microscopy of ciliary body melanoma tumor cells seeding the trabecular meshwork. E, exudate; S, sclera; TM, trabecular meshwork. |
Melanomalytic glaucoma may occur in eyes with malignant melanoma of the ciliary body. This glaucoma caused by mechanical obstruction of outflow pathways by melanin-laden macrophages was described originally by Yanoff and Scheie in 1970 in an eye with a necrotic melanoma of the ciliary body.[20] Large accumulations of macrophages engorged with melanin were seen histologically lining the anterior chamber angle and were present within the trabecular meshwork.
The differential diagnosis of glaucoma secondary to ciliary body tumors includes open- and closed-angle glaucomas. Pigmentary dispersion glaucoma, uveitic glaucoma, hemorrhagic glaucoma, neovascular glaucoma, acute angle-closure glaucoma, and chronic angle-closure glaucoma must all be considered in the differential diagnosis.
Management of glaucoma in eyes with ciliary body tumors may be carried out medically. As with iris tumors, surgical fistulizing operations are contraindicated with malignant ciliary body tumors. These procedures carry the significant risk of promoting extraocular spread of tumor cells. When malignancy is suspected clinically, enucleation is often needed in these eyes with glaucoma and ciliary body tumors and provide a histologic diagnosis of the tumor.
PRIMARY TUMORS OF THE OPTIC NERVE
Optic Nerve Melanocytoma
Melanocytomas most commonly arise within the intraocular portion of the optic nerve. A single case report has documented neovascular glaucoma associated with a melanocytoma of the optic nerve head.[34] Necrosis of the tumor resulted in occlusion of the central retinal artery and an ischemic retinal syndrome. Secondary neovascularization of the anterior segment occurred, resulting in synechial angle closure.
Management of glaucoma in eyes with melanocytomas of the optic nerve head should be conservative, with medical therapy followed by surgical therapy as needed.
PRIMARY RETINAL TUMORS
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Key Features |
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Retinoblastoma
Glaucoma may occur secondarily in eyes with retinoblastoma. The incidence of glaucoma secondary to retinoblastoma ranges from 2% to 22% in published series.[11,35] The clinical presentation of glaucoma may occur as acute angle-closure glaucoma, uveitic glaucoma, or neovascular glaucoma.
The most common mechanism of secondary glaucoma in eyes with retinoblastoma is neovascularization of the iris and angle structures with formation of peripheral anterior synechiae. Iris neovascularization is indicative of more advanced disease and is associated with a worse prognosis by histology.[36] Neovascular glaucoma accounted for 73% of glaucoma associated with retinoblastoma in one large study.[11]Histologic studies have identified neovascularization of the anterior segment in 50-59% of eyes with retinoblastoma.[37,38] Most eyes with neovascularization of the anterior segment contain large tumors involving the posterior pole with involvement of the central retinal vessels or large-branch retinal vessels.[11,35] Histologically, occlusion of these large vessels has resulted in ischemic retinopathy. The ischemic retinopathy in these eyes may secondarily cause anterior segment neovascularization. In eyes with neovascularization as the single mechanism for glaucoma, posterior pole involvement was constant.[36] Angiogenic factors from the tumor itself may also play a role in neovascularization of the anterior segment of the eye.[39]
Anterior displacement of the lens with resultant pupillary block and angle closure is the second most common mechanism, resulting in glaucoma in eyes with retinoblastoma.[11,35,37] These eyes generally have retinal detachments secondary to intraretinal or subretinal tumor with massive subretinal exudation of fluid. The space-occupying tumor and subretinal fluid displaces the lens anteriorly, resulting in pupillary block and angle closure. Massive tumor involvement of the posterior segment may cause anterior displacement of the lens-iris diaphragm to the extent of obliterating the anterior chamber, resulting in angle-closure glaucoma.
A less common mechanism of glaucoma in eyes with retinoblastoma is massive tumor involvement of the entire globe with direct involvement of the anterior chamber structures by tumor cells.[35] Seeding of the trabecular meshwork by tumor cells from posterior tumors may also occur (Fig. 209.4).[11] Many eyes with retinoblastoma have a combination of the aforementioned mechanisms, resulting in glaucoma.
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FIGURE 209.4 Anterior segment seeding by retinoblastoma with secondary glaucoma. |
The differential diagnosis of glaucoma secondary to retinoblastoma would include glaucoma associated with uveitis, persistent hyperplastic primary vitreous, retinopathy of prematurity, and other causes of neovascularization of the anterior segment. The young age of patients in whom retinoblastoma occurs helps to eliminate from the differential diagnosis many of the usual and more common causes of neovascularization of the anterior segment seen in adults. Neovascularization of the anterior segment in a child should raise the suspicion of possible retinoblastoma.
The treatment of retinoblastoma often requires enucleation of the eye for treatment of the tumor. In addition, there should be high suspicion of optic nerve invasion in the presence of secondary glaucoma and a large retinoblastoma.[40] However, in bilateral cases in which it is desirable to retain at least one eye, radiation therapy or photocoagulation may be used to treat the tumor. The management of glaucoma may then require medical therapy. Fistulizing glaucoma operations are contraindicated because of the risk of extraocular spread of tumor cells.
PRIMARY TUMORS OF THE CHOROID
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Choroidal Malignant Melanoma
Nearly 2-14% of eyes with malignant melanoma of the choroid may experience secondary glaucoma.[8,11,33] Earlier reports of the incidence of glaucoma in eyes with choroidal melanoma are higher than those found since the late 1970s. At the turn of the century and during the early 1900s, the incidence of glaucoma in eyes with choroidal melanoma was reported to be as high as 29-67%.[8-10] These differences in the incidence of glaucoma may be due to the earlier diagnosis of choroidal melanoma as a result of the routine use of the indirect ophthalmoscope since the 1960s. A recent report comparing the characteristics of choroidal melanoma in Hispanic and white patients found a higher incidence of rubeosis iridis and higher IOP in Hispanic patients.[41]
The clinical presentation of glaucoma in eyes with malignant melanoma of the choroid may be variable. High suspicion of tumor should be maintained in patients presenting with acute angle-closure glaucoma with unilateral cataract and an open nonoccludable angle in the other eye.[42] Glaucoma secondary to choroidal melanoma may also present clinically as neovascular glaucoma, chronic angle-closure glaucoma, hemorrhagic glaucoma, or uveitic glaucoma. The clinical presentation depends on the inducing mechanism.
The most common mechanism of glaucoma in eyes with malignant melanoma of the choroid is neovascularization of the anterior segment.[11] Neovascularization is seen primarily in eyes with large choroidal tumors with total retinal detachment. The association of long-standing retinal detachment and anterior segment neovascularization is well recognized. The exact mechanism, however, is not completely understood.
The second most common mechanism of glaucoma associated with choroidal melanoma is anterior displacement of the lens-iris diaphragm by the tumor mass, resulting in pupillary block with development of peripheral anterior synechiae and angle-closure glaucoma.[11,22] The angle-closure glaucoma may occur as an acute angle closure or as a more insidious chronic angle closure.
Hemorrhage within the eye secondary to the choroidal melanoma may cause glaucoma. Massive suprachoroidal hemorrhage secondary to choroidal melanoma with anterior displacement of the lens-iris diaphragm may result in angle-closure glaucoma.[11] Direct extension of tumor into the anterior chamber has resulted in hyphema with elevated IOP.
Anterior extension of a choroidal melanoma to involve the anterior segment may result in glaucoma without hemorrhage. Direct invasion of the chamber angle by tumor cells may elevate the IOP by directly involving outflow pathways.[11]
Spontaneous necrosis of choroidal malignant melanomas is known to occur. The inflammatory response in eyes with necrosis of a malignant melanoma may result in a secondary open-angle glaucoma. The presumed mechanism is obstruction of aqueous outflow pathways by inflammatory cells.[43]
Many eyes with both choroidal malignant melanoma and acquired glaucoma have large intraocular tumors and decreased vision. Often, these eyes undergo enucleation for treatment of the tumor. Management of glaucoma is therefore not an issue. However, in eyes with coexisting glaucoma and choroidal malignant melanoma that have retained good vision, the tumor may be treated with radiation or surgical resection. The elevated IOP should be managed medically.
METASTATIC TUMORS TO THE EYE AND GLAUCOMA
TUMORS METASTATIC TO THE IRIS
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Metastatic tumors involving only the iris are relatively rare. A recent review of 512 patients with uveal metastasis yielded only 40 eyes with iris metastasis.[44] Thirty-eight percent of the 40 eyes were found to have secondary glaucoma. In another large series of uveal metastasis in 256 eyes, only 11 eyes had iris metastases.[11] Seven of these eyes had elevated IOP. In a third large series of 199 metastatic carcinomas to the eye, only six involved the iris alone.[41] No specific incidence of glaucoma in these six eyes was given by the authors. The most common primary tumor sites that metastasize to the iris are the lung in males and the breast in females. Breast cancer metastasis commonly affects both the iris and the ciliary body, although lone iris involvement has been reported.[45] Cutaneous melanoma, carcinoid, kidney, colon, and prostate tumors are also known primary sites that may metastasize to the iris.[44,46,47]
The clinical presentation of glaucoma associated with metastatic disease to the iris is generally an acute process. Most commonly, the presentation is that of an acute iridocyclitis with pain, redness, and decreased vision. Elevated IOP is then found on examination. A tumor mass is often seen on the iris surface, and the tumor may be identified in the angle structures.
The most common mechanism of glaucoma in eyes with metastatic disease to the iris is direct invasion of the aqueous outflow pathways by tumor cells.[11,47] Squamous cell carcinoma metastatic to the iris and anterior segment may form an 'epithelial-like' lining over the anterior chamber structures that is similar to epithelialization of the anterior chamber after anterior segment surgery,[46] and desquamated tumor cells or keratin debris may also block outflow.[48] Less commonly, hyphema from an iris metastasis may result in hemolytic glaucoma.[11]
The differential diagnosis of glaucoma secondary to metastatic disease to the iris includes glaucoma associated with uveitis, hyphema, iris cysts, and primary iris tumors. Medical management of glaucoma associated with iris metastasis is appropriate. Radiation of metastatic lesions may also be useful as may chemotherapy to treat the systemic tumor. Enucleation may be necessary when there is intractable pain secondary to glaucoma.
A unique and rare 'black hypopyon' and secondary glaucoma may occur in eyes with cutaneous melanoma metastatic to the iris.[49,50] Free-floating melanoma tumor cells and pigment-laden macrophages have been documented to form the 'black hypopyon'. It is postulated that these tumor cells and macrophages mechanically obstruct aqueous outflow pathways.
TUMORS METASTATIC TO THE CILIARY BODY
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Metastatic disease isolated to the ciliary body is rare. In one series of 199 cases of metastasis to the eye, none was completely isolated within the ciliary body.[46] Twenty of the 199 cases involved both the ciliary body and the iris, with nine of the 20 predominantly involving the ciliary body. A second study of 256 eyes with uveal metastases revealed three eyes with metastasis to the ciliary body.[11] Two of the three eyes had secondary elevation of IOP.
The clinical presentation of glaucoma secondary to ciliary body metastasis is similar to that associated with iris metastasis. In general, an acute iritis is seen with an associated elevation of IOP and a tumor involving the anterior chamber angle. The most common primary tumor site is usually the lung or the breast, such as with iris metastasis.[46]
Direct extension of a tumor from the ciliary body into the anterior chamber and involving the angle structures is the most common mechanism of secondary glaucoma in tumors metastatic to the ciliary body.[11,46] Hemorrhagic glaucoma, neovascularization of the anterior chamber, and mechanical angle closure resulting from forward displacement of the iris-lens diaphragm by tumor are other mechanisms by which glaucoma may occur in eyes with metastasis to the ciliary body.[46]
Management of glaucoma secondary to ciliary body metastasis is similar to that of glaucoma associated with iris metastasis. Medical therapy to control the IOP along with radiation therapy or chemotherapy to treat the tumor may all be beneficial. Enucleation may be performed for uncontrolled glaucoma that produces pain.
TUMORS METASTATIC TO THE CHOROID
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The posterior choroid is the most common site within the eye to which tumors metastasize.[47] In published series, 74-94% of uveal metastases involve the choroid.[11,47] Breast carcinoma accounts for most metastatic disease to the choroid.[47] Lung carcinoma is the second most common primary tumor to metastasize to the choroid.[47] In male patients, a lung tumor is the most frequent tumor involving the choroid, compared with breast carcinoma in females.[47] Kidney, testicle, prostate, pancreas, colon, and other gastrointestinal tumors are all known to metastasize to the choroid.[11,47,51] Glaucoma associated with metastasis to the choroid is rare in comparison with glaucoma associated with metastasis to the anterior uveal tract. In one large series, glaucoma associated with metastasis to the choroid occurred in only 1% of eyes.[11] This percentage is strikingly different from that in eyes with metastasis to the iris or ciliary body, which have an incidence of glaucoma as high as 56-64%.[11,46]
Angle-closure glaucoma is the most common form of glaucoma in eyes with metastasis to the choroid.[11] Angle-closure glaucoma is produced in eyes with metastasis to the choroid by anterior displacement of the iris-lens diaphragm. Serous retinal detachment or choroidal detachment often contributes to anterior displacement of the iris-lens diaphragm.
Glaucoma secondary to metastasis to the choroid may be managed by medical means to lower IOP. Radiation to the metastatic lesion along with chemotherapy may also be appropriate to treat the metastatic tumor. Enucleation is required for glaucoma associated with intractable pain.
MISCELLANEOUS TUMORS INVOLVING THE EYE AND GLAUCOMA
GLAUCOMA SECONDARY TO LEUKEMIA
The ocular manifestations of leukemia are well described.[52] The eyes may be involved in both acute lymphocytic leukemia and chronic lymphocytic leukemia. Leukemic involvement of both the posterior and anterior segments of the eye has been reported. The incidence of ocular involvement in leukemia ranges from 50% to 80% of eyes in published studies.[52,53] Despite frequent ocular involvement by leukemia, glaucoma secondary to leukemia is relatively rare. When glaucoma is present, it is most often secondary to anterior segment involvement.
Anterior segment involvement of leukemia may present as a conjunctivitis, iris heterochromia, iritis, hyphema, and pseudohypopyon.[52] An unusual clinical presentation of bilateral glaucoma and proptosis has also been reported.[54] Elevated IOP may occur in eyes with leukemic involvement of the anterior segment secondary to iritis, hyphema, or pseudohypopyon consisting of leukemic cells. Leukemic infiltrates involving the trabecular meshwork and tissue surrounding Schlemm's canal has been documented histopathologically in eyes with elevated IOP.[55,56] Epibulbar leukemic infiltrates of the bulbar conjunctiva and episcleral tissue may involve aqueous veins.[57] Epibulbar leukemic infiltrates have been implicated as a mechanism by which secondary glaucoma may occur in eyes with leukemic involvement.
Management of the glaucoma may be by medical means to control the IOP. Radiation therapy or chemotherapy to treat the underlying tumor may also promote resolution of the glaucoma.[52,55,57]
GLAUCOMA SECONDARY TO MULTIPLE MYELOMA
The ocular manifestations of multiple myeloma are well known.[58] One of the prominent features are cysts of the pars plana and ciliary body. The ciliary body cysts have been implicated in the dislocation of the crystalline lens, with resultant lens-induced angle-closure glaucoma. Forward displacement of the iris root by ciliary body cysts has also been implicated in secondary angle-closure glaucoma associated with multiple myeloma.[59]
The presentation of glaucoma secondary to multiple myeloma may be that of acute or chronic angle closure. If the mechanism is found to be lens-induced angle closure, removal of the lens may be curative. If the mechanism is direct forward displacement of the iris root, medical therapy to lower IOP should be used. Laser iridectomy or laser cyst puncture may be useful in managing secondary angle-closure glaucoma due to ciliary body cysts.
GLAUCOMA SECONDARY TO LARGE-CELL LYMPHOMA
Large-cell lymphoma (reticulum cell sarcoma) may occur in the eye and masquerade as a unilateral or bilateral uveitis. The diagnosis is made by biopsy of the vitreous for cytologic studies to document the presence of lymphoma cells. Diffuse infiltration of the uveal tract by large-cell lymphoma has resulted in an acute glaucoma secondary to closure of the angle by necrotic swollen iris tissue.[60] Glaucoma secondary to chronic intraocular inflammation, with and without chronic angle closure, has been reported to occur in eyes with large-cell lymphoma.[61,62] Intraocular lymphoma may also result in elevated IOP by tumor cells seeding the anterior chamber angle.[11] The tumor is best treated with radiation therapy. The glaucoma should be managed by medical means.
GLAUCOMA SECONDARY TO JUVENILE XANTHOGRANULOMA
Juvenile xanthogranuloma is a benign histiocytic proliferation affecting the skin and eye seen in infants and young children. Typical skin lesions of the disease are yellow-orange papules found on the skin of the head and neck.
Ocular manifestations are most commonly seen in the anterior segment as an iris tumor that is lightly pigmented or salmon colored.[63] Spontaneous hyphema often occurs in the presence of iris involvement. Juvenile xanthogranuloma is the most common cause of spontaneous hyphema in children. Typical skin lesions may not be present, even with ophthalmic involvement.[63,64] The presentation is often acute with a red and painful eye. On examination, hyphema, iris tumor, and elevated IOP are found.[63,64]
Glaucoma may occur by several mechanisms in eyes with juvenile xanthogranuloma. Direct involvement of the iris and adjacent angle structures by proliferating histiocytes may obstruct aqueous outflow.[63]Glaucoma may also develop after recurrent spontaneous hyphemas.[63,64] Resolution of glaucoma secondary to juvenile xanthogranuloma may occur after treatment of the tumor by topical or systemic steroids.[64-67] Low-dose radiation therapy to involved iris tissue has also promoted resolution of the tumor and the associated glaucoma.[64,66]
GLAUCOMA SECONDARY TO HISTIOCYTOSIS
Histiocytosis X is a proliferation of histiocytes that typically involve multiple organ systems. A secondary open-angle glaucoma has been associated with histiocytosis X.[68] Aspiration demonstrated that histiocytes were present in the aqueous. These histiocytes were implicated as a mechanism of obstruction of aqueous outflow.
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