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

420 Glaucoma Associated with Intraocular Tumors

Treatment and Management

How Is Glaucoma Associated with Intraocular Tumors Treated?

IRIS MELANOMA

A newly diagnosed iris melanoma is often managed by observation, and the glaucoma is conservatively managed with medical therapy. Slit-lamp photography and gonioscopy are essential to document growth of the lesion. Laser trabeculoplasty to the uninvolved meshwork can be performed if more aggressive treatment is required.3 Shields and Proia51 describe regression of neovascular glaucoma after excision of an iris melanoma. A diffuse or large iris melanoma may require enucleation. Filtration surgery is contraindicated due to the risk of dissemination or extrascleral extension.

CILIARY BODY AND CHOROIDAL MELANOMA

Uveal melanomas associated with glaucoma are typically large, diffuse, and associated with a poor prognosis. Therefore, enucleation is usually the standard of care. Intraoperatively, care must be taken to avoid iatrogenic elevation in the IOP, thereby risking tumor dissemination.78–80 Several authors report that enucleation may decrease the patient’s prognosis for survival. Within the group of patients with uveal melanoma, peak mortality occurs 2 years after enucleation and is associated with a 12% mortality rate. In contrast, nonenucleated patients exhibited a mortality rate of 1% per year of life. Contrasting these two melanoma patients groups, the mortality rate of the enucleated group equals that of the nontreated group at 7 to 8 years. Fraunfelder et al81 have recommended the “no touch” technique during an enucleation to minimize the elevated IOP spike to 500 mm Hg, causing tumor cells to disseminate systemically and increasing the incidence of metastasis.81

Although glaucoma secondary to melanoma does not usually respond to medical treatment,52 a trial of glaucoma medications is warranted. In rare cases, local excision or irradiation techniques may be employed. Ophthalmic oncologists may best perform radioactive plaque therapy. Surgical treatment with filtering surgery is contraindicated due to the risk of dissemination, extrascleral extension, or even metastases.82 For intractable glaucoma that is medically uncontrollable, a cyclodestructive procedure or enucleation may be indicated for large melanomas. Kim et al83 utilized helium ion irradiation predominantly to treat mostly large uveal melanomas. Patients with large melanomas who received higher radiation doses tended to develop neovascular glaucoma in contrast to patients who received low irradiation doses.

The Collaborative Ocular Melanoma Study (COMS) is an ongoing international study to evaluate small, medium, and large melanomas. Large melanoma is a potential metastatic tumor associated with patient mortality; this randomized study will evaluate the mortality rate of patients treated with enucleation alone versus external beam radiation and subsequent enucleation.84 Prior to any surgical intervention, it is important to have the patient evaluated by a medical internist and to obtain some ancillary studies. These studies include a complete blood count, liver function studies, and chest x-ray. If the liver function studies

are abnormal, CT, MRI, or fine-needle liver biopsy may be necessary to evaluate the presence of metastatic disease. Following treatment of an intraocular melanoma, the patient should be periodically evaluated systemically for potential metastatic disease.

METASTATIC CANCER AND LEUKEMIA

Treatment of metastatic cancer or leukemia with chemotherapy and possible local irradiation to the eye often results in resolution of the glaucoma. If the IOP remains elevated, the residual glaucoma can be treated medically, with cyclodestructive surgery or retrobulbar alcohol. Blind, painful eyes are enucleated. An incidental report describes washing necrotic tumor cells from the anterior chamber to treat glaucoma associated with leukemia.56 Semiconductor diode laser transscleral cyclophotocoagulation was described by El-Harazi et al.85 This case report described a patient with progressive infiltrative ductal carcinoma of the breast with metastasis to the brain, spine, liver, lung, and iris. This associated elevated IOP was refractory to maximal tolerated medications. The patient received contact transscleral semiconductor diode laser cyclophotocoagulation and subsequent external beam radiation; within 2 months the IOP was controlled, but the iris metastatic lesions did not resolve. In summary, diode laser has been used in refractory glaucoma but the risk of tumor dissemination is unknown.85

RETINOBLASTOMA

Glaucoma associated with retinoblastoma usually occurs in the context of a unilateral advanced and large tumor. Therefore, enucleation is performed when a long section of optic nerve is obtained for histologic examination for metastatic or direct extention. In the presence of bilateral retinoblastoma, episcleral plaque radiotherapy or external beam irradiation may be an alternative in selected cases. Because preservation of useful vision is imperative, consultation with an ophthalmic oncologist is prudent. A detailed family history and exam under anesthesia (EUA) with funduscopy is important prior to enucleation. A lumbar puncture, bone marrow aspirate, and bone marrow biopsy should be obtained during the EUA to exclude metastases via cerebrospinal fluid and hematogenous extention. Additional ancillary studies may include a bone scan to identify distant metastases and a CT to document the presence of intraocular calcium and pinealoblastoma. Genetic evaluation and counseling are important to determine if the form of retinoblastoma is of hereditary nature. Because retinoblastoma is associated with a deletion of the second allele of the long arm of chromosome 13 (13q14), tumor suppressor gene product is not produced and these individuals are susceptible to secondary tumors such as osteosarcoma, malignant melanoma, chondrosarcoma, rhabdomyosarcoma, glioma, neuroblastoma, squamous cell carcinoma, and sebaceous cell carcinoma.86–91

JUVENILE XANTHOGRANULOMA

This is a benign and often self-limiting disease that responds to topical, subconjunctival, and systemic steroids. Rarely, external beam irradiation is

422 Glaucoma Associated with Intraocular Tumors

required. Trabeculectomy has not proven to be successful. Medical and not surgical treatment of the glaucoma should be attempted.92–94

MEDULLOEPITHELIOMA

Treatment of medulloepithelioma has not been standardized.6 These frequently blind and painful eyes undergo enucleation. Small, well-circum- scribed tumors may be locally resected by cyclectomy, iridocyclectomy, or iridocyclotrabeculectomy.

MELANOCYTOMA

Melanocytoma treated with excisional biopsy may undergo normalization of the IOP.23 Shields et al23 described management of a case in this manner but caution that pigmented iris lesions associated with glaucoma may be difficult to differentiate from malignancy. Even benign tumors may undergo necrosis, and the decision to enucleate may be justifiable.

STURGE-WEBER

The glaucoma associated with Sturge-Weber syndrome may initially be managed medically but frequently requires more definitive surgery later. Filtering surgery is associated with increased frequency of complications such as choroidal effusion or even expulsive choroidal hemorrhage. Some authors recommend preplaced sclerostomies or combined trabeculectomy/trabeculotomy to reduce the chance for complications.95–97

NEUROFIBROMATOSIS

Neurofibromatosis associated glaucoma should be treated medically when possible, as the response to surgery is often poor.98

Future Considerations

Active research is being pursued in the treatment of retinoblastoma and choroidal melanoma in animal models and in limited human studies.

Murine models can be transgenically induced to produce retinoblastoma. Carney et al99 have suggested that frequent subconjunctival carboplatin may be effective. The total dose of this drug appears to be important in tumor control in the murine transgenic retinoblastoma model. These data may also have significant clinical implications for the treatment of childhood retinoblastoma. Furthermore, Cicciarelli et al100 studied the toxicity of subconjunctival injected carboplatin by monitoring the electroretinogram (ERG) and subsequent histologic changes in dwarf pigmented rabbits. This study suggests that subconjunctival carboplatin may be well tolerated in the treatment of retinoblastoma.

Stereotactic radiotherapy and radiosurgery may be beneficial in the treatment of uveal melanoma. Zehetmayer et al101 utilized stereotactic Linac-based radiotherapy (linear accelerator) to irradiate uveal melanoma. This treatment may play a role in the conservative management of uveal melanoma. Mueller

et al102 studied the efficacy of stereotactic radiosurgery of uveal melanoma with the Leksell gamma knife. Although only 25 patients were included in this short-term study, results indicate that radiosurgery using the Leksell gamma knife was beneficial in medium-size and large choroidal body melanomas that otherwise would be enucleated. These studies did not specifically discuss the issue of glaucoma associated with retinoblastoma or melanoma. However, these future medical and surgical modalities may facilitate visual acuity preservation and control of elevated IOP.

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