INTRAOCULAR TUMORS

 

INTRODUCTION:

A number of intraocular tumors and tumor-like disorders are responsible for the development of glaucoma. In a survey of 2597 patients with intraocular tumors, 5% of the eyes were reported to have tumor induced elevated intraocular pressure (IOP) at the time of tumor diagnosis.

The common tumors associated with secondary glaucoma include, choroidal melanoma, ring melanoma of the ciliary body, iris melanoma, retinoblastoma and large-cell lymphoma.

 

In case of malignant intraocular tumors, it is more imperative to preserve life rather than focusing on glaucoma management. However, in benign tumors the consideration is on avoiding loss of vision from unnecessary treatment.

Glaucoma secondary to intraocular tumors should be considered in all cases of unilateral or heavily asymmetric glaucoma, particularly when certain features such as iris heterochromia, lack of response to IOP-lowering treatment, or lack of response to steroids, which may indicate pseudouveitis, are present.

Occasionally, the intraocular tumor may not be easily diagnosed as it is obscured by cataract, vitreous hemorrhage or retinal detachment. In such situations, investigations such as ultrasound B-scan, ultrasound biomicroscopy (UBM) and CT-scan/MRI can prove useful.

The pathophysiology of pressure elevation in eyes with intraocular tumors is through open angle as well as closed angle mechanisms. Blockage of the angle by tumor cells may cause open angle glaucoma. The mechanism of angle-closure glaucoma is determined by the size, location, and pathology of the tumor.

Management of secondary glaucoma in such cases is largely pharmacological or by external cyclodestructive methods.

PRIMARY UVEAL MELANOMAS:

Melanomas of the uveal tract, the most common primary intraocular malignancy, are frequently associated with glaucoma by several mechanisms and with a variety of clinical presentations. In one large histopathologic study of eyes with malignant melanomas involving one or more portions of the uveal tract, the overall prevalence of glaucoma was 20%.

 

Anterior uveal melanomas lead to IOP elevation more frequently than posterior melanomas, with reports of 41% and 45% of patients in two series, and choroidal melanomas were found to have associated glaucoma in 14% in one study. In another study, 3% of 2111 eyes with uveal melanomas had associated IOP elevation, including 7% with iris melanomas, 17% with ciliary body melanomas, and 2% with choroidal melanoma.

Melanomas of the anterior uvea may manifest as unilateral glaucoma. They may lead to glaucoma by open-angle or angle-closure mechanisms; the former mechanism is more common. Aqueous humor outflow in the open anterior chamber angle can be obstructed by direct extension of the tumor or by trabecular meshwork seeding by tumor cells or melanin granules.

In some eyes, the melanoma may arise from the iris, ciliary body, or iridociliary junction and spread circumferentially, creating a ring melanoma. A review of 14 patients with ring melanoma of the anterior chamber angle found that all patients presented with elevated IOP in the affected eye. Occasionally, a ring melanoma can masquerade as pigmentary glaucoma. Patients with ciliary body melanomas can present with chronic uveitis and refractory glaucoma. In melanomalytic glaucoma, macrophages containing melanin from a necrotic melanoma obstruct the trabecular meshwork.

Another variation of anterior uveal melanoma and glaucoma occurs with a tapioca iris melanoma. This rare melanoma of the iris creates a nodular appearance resembling tapioca pudding and typically consists of low-grade spindle-type cells, although a case with epithelioid-type cells and metastases has been reported. Glaucoma is reported to occur in one-third of the cases with tapioca melanoma.

An alternate mechanism of IOP elevation with an iris melanoma is neovascular glaucoma, which may resolve after excision of the tumor. Tumors produce a tumor-angiogenesis-factor which causes rubeosis iridis, leading to the development of neovascular glaucoma.

Ciliary body melanomas may also cause an angle-closure form of glaucoma due to compression of the root of the iris into the anterior chamber angle or forward displacement of the lens-iris diaphragm.

It needs to be emphasized that conditions such as iritis or iris cysts may masquerade as intraocular tumors with secondary rise of IOP.

Prognosis:

When a uveal melanoma is associated with glaucoma, the prognosis appears to be worse for metastasis and death, compared with that for a melanoma without glaucoma. In one study, three of four patients with a primary melanoma of the ciliary body and glaucoma died of metastatic disease within 2.5 years after enucleation, and another investigation of uveal melanomas in children and adolescents identified glaucoma as a predominant factor relating to a fatal outcome.

The presence of glaucoma with an iris melanoma may also increase the risk for metastasis.

Management:

Ciliary body or choroidal melanoma associated with glaucoma carries a poor prognosis, and the recommended management most often is enucleation. In appropriate cases, fine-needle aspiration biopsy can be considered first to confirm the presence of malignancy. Once glaucoma develops, the melanoma is usually too large or diffuse for local treatment. In selected cases local excision such as iridocyclectomy can be done. Radiotherapy to shrink the tumor often does not completely treat the tumor and the inflammation may cause further rise in IOP.

Iris melanoma and glaucoma are usually managed more conservatively because the tumors are typically small when first detected and can be observed for evidence of growth. However, iris melanomas may metastasize, and the degree to which associated glaucoma increases this risk is uncertain.

In managing the associated glaucoma in eyes with a uveal melanoma, it is best to limit the therapeutic options to medical therapy. Filtering surgery should be avoided, as seeding of iris melanoma cells through a trabeculectomy site into the filtering bleb with extraocular dissemination and fatal metastases have been documented. When additional intervention for the glaucoma is required, especially in eyes with iris melanomas, an ab externo cyclodestructive procedure may be the procedure of choice. [Shields]

METASTATIC GLAUCOMA:

Metastasis of the anterior segment ay give rise to secondary glaucoma. In one study of 227 cases of carcinoma metastatic to the eye and orbit, glaucoma was detected in 7.5% of the total group and in 56% of the 26 cases with anterior ocular metastasis. In another series of 256 eyes with uveal metastases, associated IOP elevation was present in 5% of the total group but in 64% and 67% of eyes with iris and ciliary body metastases, respectively.

Mechanisms of glaucoma in eyes with anterior uveal metastatic carcinoma include obstructions of the trabecular meshwork by sheets of tumor cells or by infiltration with neoplastic tissue. Other mechanisms include angle closure due to compression of the iris from the tumor or by peripheral anterior synechiae. Although ocular melanomas usually are primary malignancies, metastatic melanomas of the eye occur and can occasionally cause glaucoma. A unique form has been called black hypopyon, in which a disseminated cutaneous malignant melanoma metastasized to the eye, where it became necrotic, possibly in response to immunotherapy or irradiation, resulting in a hypopyon of tumor cells and pigment-laden macrophages with associated glaucoma.

Other causes of secondary glaucoma include leukemic infiltration of the anterior segment, and is often associated with raised IOP and presents with hypopyon or subretinal hemorrhage. Certain childhood tumors such as retinoblastoma, medulloepithelioma, and rhabdomyosarcoma may also cause rise in IOP. Another important cause of such a condition is Sturge-Weber Syndrome. This condition has been dealt with elsewhere on The Glog. https://theglog2.blogspot.com/2021/01/sturge-weber-syndrome.html

Prostaglandin analogs are usually the first choice of drugs for the pharmacologic treatment of glaucoma. However, in cases of iris melanocytic tumors, there is a theoretical risk of increased pigmentation of the iris/tumor, following such therapy. This may lead to a false appearance of increase in size of the tumor. 

Prostaglandin analogs, Rho-kinase inhibitors and cholinergic agents increase trabecular and uveoscleral aqueous outflows. This could probably increase the risk of blood-borne metastasis of the malignancy. However, studies performed so far have not verified such claims.

CONCLUSION:

Masquerade syndromes are often associated with secondary glaucoma. In suspected cases appropriate investigations should be done to rule out such causes of raised IOP. These situations can even turn out to be life-threatening.