Ординатура / Офтальмология / Английские материалы / Neuro-Ophthalmology_Kidd, Newman, Biousse_2008

or no significant intracranial extension of the tumor. In such cases, a clinical examination, including assessment of visual acuity, color vision, and visual fields should be conducted twice a year for 2 to 3 years, then once a year if the patient’s visual function has remained stable. Patients should be counseled to contact their physician if they note any visual loss in the interim. Neuroimaging at 6-month intervals is appropriate for the first 1 to 2 years, then once a year for 2 to 3 years and then every 3 to 4 years, assuming that the clinical examination is stable.56,57 Because younger patients are more likely to have larger or more rapidly developing tumors, children and young adults with presumed ONSMs should be followed both clinically and with neuroimaging at more frequent intervals.

Several series have been published describing SFR as a primary treatment option for ONSMs.29,51,55,58–61 The data from these studies, including visual

outcomes, are summarized in Table 9–1. Summarizing the data from all seven series, the overall disease control in 75 patients was 94.6%. Improvement of visual function occurred within the first 3 months after treatment in 54.7% of the patients. None of the patients had neuroimaging evidence of tumor enlargement during the period of follow-up, and, in fact, a few patients had imaging evidence of a slight decrease in tumor volume. Acute effects of SFR included headache, nausea, local erythema, and focal alopecia. None of these complications were severe or permanent; however, radiation retinopathy was observed in two patients 4 years after treatment. The retinopathy was severe in one and was associated with vitreous hemorrhage,61 whereas the other patient had only retinal microaneurysms.55 This latter patient had a large tumor involving the proximal optic nerve adjacent to the globe, and portions of her retina received 54 Gy. Even so, her vision improved from 20/50 and remained stable at 20/25. In a more recent report,62 radiation retinopathy occurred 22 months after SFR, resulting in loss of vision from 20/25 to 20/200. The posterior retina in this patient had received 27 to 48 Gy.

Other late ophthalmic complications of SFR included cataract in one patient, dry eye in one, and iritis in two. None of the patients developed radiation optic neuropathy; however, two patients continued to lose vision, thought to be from tumor progression.

Late nonocular side effects reported in these studies included late pituitary dysfunction in three patients and radiologically evident cerebral punctate smallvessel fallout in one. Both are a potential concern after irradiation for posteriorly located ONSMs, particularly those with mild but definite intracranial extension. Interval monitoring of pituitary function in such patients thus is appropriate.

As noted previously, in rare cases of anteriorly located, primarily exophytic tumors with focal involvement of the dural sheath, surgical excision is a potential treatment choice and can be performed without undue risk of iatrogenic visual loss.29,54 Optic nerve sheath decompression with release of trapped cerebrospinal fluid or removal of soft tumor followed by radiation therapy may also be beneficial in cases of acute visual loss63; however, extensive removal of ONSMs that extend for some distance within the optic nerve sheath or are located in the posterior orbit and/or optic canal is generally indicated only in rare cases in which there is aggressive tumor growth or disfiguring proptosis. Along with unavoidable and permanent blindness, such procedures may also cause temporary or permanent ophthalmoparesis, ptosis, or both.

The main goals in the management of ONSMs are ensuring a favorable visual outcome, establishing local control of the tumor, and minimizing the risks of

treatment-related morbidity. Limitations for any treatment study of ONSMs include both the rarity and usually very slow course of the disease, the fact that there often is no tissue diagnosis so that some patients in a treatment trial could have lesions other than an ONSM (e.g., sarcoid of the optic nerve), the necessity of pooling of data from multiple different treatment centers, and the need for a long (>10 years) follow-up period to detect late recurrences and late side effects of the treatment.

In the seven studies described previously, the short-term efficacy of SFR in preserving or improving vision appears to be excellent, with more than half of the patients having an improvement within 3 months following treatment. The results also suggest that earlier treatment might offer a better chance of preserving useful vision. Based on the results of published studies as well as our own experience, we believe that SFR is the best option for most cases of progressive or advanced disease. However, because of increasing early diagnosis, more and more patients with presumed ONSMs associated with mild progressive or stable visual loss are being diagnosed, and the decision as to whether to observe or treat is much less clear. Longer follow-up to establish the incidence of late toxicity following SFR will be needed to clarify the optimal management of these cases.

SCHWANNOMA

Schwannomas are benign tumors that arise from Schwann cells in the peripheral nervous system. Although the most common sites are the vestibular division of

the eighth cranial nerve and the trigeminal nerve root, schwannomas occasionally involve the optic nerve.64–66 Because optic nerve myelin is produced by oli-

godendrocytes rather than Schwann cells, these tumors probably arise from the Schwann cells that accompany the sympathetic nerves that are tightly adherent to the optic nerve sheath.67

The microscopic appearance of schwannomas of the optic nerve is the same as for all schwannomas of peripheral nerve origin, thus distinguishing them from similar appearing lesions, such as optic nerve gliomas or meningiomas; however, the clinical presentation of these lesions is nonspecific. They have been reported in both children and adults, all of whom have developed progressive visual loss associated with evidence of an optic neuropathy and variable proptosis.

Optic nerve sheath schwannomas probably cannot be diagnosed on clinical grounds alone, and their neuroimaging appearance mimics that of the more common optic nerve gliomas (Fig. 9–14). Instead, in the reported cases, the diagnosis has been made at surgery. To date, surgery has been the treatment of choice, but in view of the increasing tendency to treat many intracranial schwannomas with stereotactic radiosurgery, this treatment option perhaps should be considered for schwannomas of the optic nerve.

HEMANGIOPERICYTOMA

Hemangiopericytomas are composed of the pericytes of blood vessels (Fig. 9–15). They may develop in virtually any tissue in the body that has capillaries. It was once thought that hemangiopericytomas were actually a type of angioblastic

Figure 9–14 Optic nerve sheath schwannoma. A, Computed tomography appearance. B, Histopathology.

A

Figure 9–15 Histopathology of optic nerve sheath hemangiopericytoma. A, Relationship of tumor to dural sheath. B, Higher power of tumor cells. (Courtesy of Dr. W. Richard Green.)

meningioma that arose from the vascular elements of the pia mater. Ultrastructural studies, however, have led to a better understanding of the histogenesis of these tumors. By light microscopy, hemangiopericytomas are composed of a monomorphous proliferation of plump or spindle-shaped cells. Ultrastructurally, the pericytes show varying degrees of differentiation into smooth muscle cells, glomus cells, endothelial cells, and fibroblasts.

Hemangiopericytomas, unlike meningiomas, have no sex predilection. They usually become symptomatic in the fifth decade of life and usually are painless and enlarge slowly.

Figure 9–16 Computed tomography appearance of an optic nerve sheath hemangiopericytoma. (Courtesy of Dr. R.L. Font.)

I am aware of a single case of a hemangiopericytoma of the optic nerve sheath.68 The patient was a 61-year-old man who experienced progressive visual loss in the right eye following a systemic viral illness. He was thought to have optic neuritis, but the visual loss worsened considerably of the next few months and a CT scan showed a focal fusiform enlargement of the orbital portion of the right optic nerve thought to be consistent with an optic nerve sheath meningioma (Fig. 9–16). The patient subsequently underwent exploration of the right orbit at which time the abnormal portion of the optic nerve was excised. Pathologic examination of the specimen revealed an intradural hemangiopericytoma compressing an otherwise normal optic nerve.

The treatment of choice for hemangiopericytomas is complete surgical excision. The roles of both radiation therapy and chemotherapy are controversial.

Secondary Tumors

The most common secondary tumors that infiltrate the optic nerve are metastatic and locally invasive carcinomas and various lymphoreticular malignancies, particularly lymphoma and leukemia.

METASTATIC AND LOCALLY INVASIVE TUMORS

The optic nerve may be the site of metastasis from distant tumors or of spread of tumor from a contiguous structure. Metastases can reach the optic nerve by one

of four routes: from the choroid, by vascular dissemination, by invasion from the orbit, and from the central nervous system (CNS).69–72 Regardless of the mode

of spread, the substance of the nerve is affected more often than the sheath. In one large series, metastases to the optic disc occurred in 30 of 660 (4.5%) patients with ocular metastases.73 The disease occurs more often in women.

Patients with metastases to the optic nerve usually have evidence of an optic neuropathy. The visual loss is usually severe, but relatively normal vision may be present in the early stages. Any type of field defect may be present. A relative

Most patients with metastatic tumor to the optic nerve already have a known diagnosis of a primary carcinoma with other evidence of metastases at the time that visual loss occurs. This makes the diagnosis relatively straightforward, whereas most patients with a tumor that spreads contiguously to the optic nerve are not known to harbor a tumor when they first experience loss of vision. Nevertheless, any person with known cancer in another part of the body, with or without other evidence of metastases, who develops an optic neuropathy should be suspected of having cancer as the cause until proven otherwise. Similarly, any patient with a basal skull tumor who develops an optic neuropathy should be assumed to have spread of tumor to the optic nerve, unless there has been previous radiation therapy to the region, in which case the possibility of radiation-induced optic neuropathy must also be considered.

Contiguous spread of primary tumors from the paranasal sinuses, nasophar-

ynx, brain, and adjacent intraocular structures to the optic nerve occurs much less often than does metastasis to the nerve.85–89 In most cases, the tumor invades

the posterior orbit or cavernous sinus, producing a syndrome that is characterized by loss of vision, diplopia, ophthalmoparesis, and trigeminal sensory neuropathy.87 Unusual examples of such occurrences include a case of an esthesioneuroblastoma presenting with unilateral blindness in an 11-year-old girl90 and a case of adenoid cystic carcinoma of the lacrimal gland producing a steroid-responsive optic neuropathy.91

Even less common than cases of metastatic or locally invasive tumors of the optic nerve, are cases of “tumor within a tumor” (“collision tumors”). Renal cell carcinoma seems to be the recipient or host tumor that most commonly “attracts” other cancers, with lung carcinoma being the most common primary tumor to metastasize to the site.92

Neuroimaging should be performed in all patients suspected of having infiltration of the optic nerve by cancer. CT scanning typically shows an enhancing nerve that may or may not be enlarged. On MRI, either a circumscribed area of

optic nerve enlargement is identified93 or, more commonly, the nerve is usually diffusely enlarged similar to a meningioma74,80,94 (Fig. 9–18) and may show

varying T1 and T2 values that are presumed to be related to associated hemorrhage or exudates. Tumors with a tendency to metastasize to bone, such as prostate and carcinoma, can present with optic canal involvement and a retrobulbar optic neuropathy.95

Figure 9–18 Magnetic resonance imaging appearance of infiltration of optic nerve by metastatic breast carcinoma in a 57-year-old woman. Axial view shows massive enlargement of the right optic nerve with flattening of the posterior pole of the right eye.

Most metastatic optic nerve tumors show at least temporary response to radiation therapy. Tumors that spread contiguously to the optic nerve from the base of the skull or paranasal sinuses are typically less radiosensitive than metastatic tumors and also tend to be less responsive to chemotherapy.

Meningeal tumor cuffing or direct infiltration of the optic nerve can cause loss of vision in the setting of meningeal spread of carcinoma.96–98 This phenomenon is called meningeal carcinomatosis. The optic neuropathy that occurs in the setting of meningeal carcinomatosis is usually associated with a “diagnostic quartet” that consists of (a) headaches typical of raised intracranial pressure, (b) blindness,

(c) sluggish or absent pupillary reflexes, and (d) normal-appearing optic discs.99

The frequency of optic nerve involvement in patients with carcinomatosis of the meninges varies from 15% to 40%.100–103 Patients who develop meningeal

carcinomatosis with visual loss may do so after the primary lesion, usually in the lung or breast, has already been diagnosed. In other cases, visual loss may occur coincident with other signs of chronic meningitis104 or as an isolated finding as the first sign of disease.105 Although blindness may begin in one eye, both eyes are usually affected within a short time. In rare instances, visual loss remains strictly unilateral.106 A similar presentation has been described in patients with germinomas and vision loss resulting from secondary optic nerve seeding through the cerebrospinal fluid.107

Histopathologic examination of cases with meningeal carcinomatosis and blindness generally shows marked cuffing of the subarachnoid space of the optic nerve by sheets of malignant cells, with little invasion of the nerves themselves. Thus, in some cases, there is true infiltration, whereas in other cases, the lesion is more compressive than infiltrative.

LYMPHORETICULAR TUMORS

Infiltration of the retrobulbar optic nerve, optic chiasm, or both can occur in patients with both Hodgkin’s disease and non-Hodgkin’s lymphoma (NHL).108–120

In most of these cases, the infiltration occurs from spread of CNS tumor; however, in some cases, there is infiltration of the optic nerve, apparently from extension of tumor from the adjacent maxillary and sphenoid sinuses.121

In many cases of lymphomatous infiltration of the anterior visual sensory pathway, the patient is known to have NHL or Hodgkin’s disease at the time visual

signs and symptoms develop, and the diagnosis is not in doubt.111 In other cases, however, the visual loss is the presenting sign of the disease108,110,113,122 or

an isolated manifestation of disease recurrence.114

The symptoms and signs of patients with lymphomatous infiltration of the optic nerve depend on the location and extent of the lesion. In some cases, the visual loss

is insidious in onset and slowly progressive.116 In other cases, the visual loss is acute and mimics optic neuritis or ischemic optic neuropathy.110,114,115 Secondary

retinal vein and retinal artery occlusions have been described in conjunction with lymphomatous infiltration of the optic nerve.120,123 Successful treatment has been

reported using steroids, chemotherapy, radiation therapy, or a combination of these modalities.

The appearance of optic nerve infiltration by lymphoma is nonspecific. With CT scanning, the infiltrated nerve appears enlarged, has increased density, and enhances after intravenous injection of iodinated contrast material. With MRI,

A B

Figure 9–19 Neuroimaging appearance of infiltration of the both optic nerves by a B-cell lymphoma. A, Noncontrast, T1-weighted, coronal magnetic resonance imaging (MRI) shows enlargement of intracranial portion of right optic nerve (arrowhead). B, After intravenous injection of gadolinium, T1-weighted, coronal MRI shows enhancement of both the right and left optic nerves

(arrowheads).

the same structure can be isointense, hyperintense, or hypointense on T1weighted images; is hyperintense on T2-weighted MR images; and enhances after intravenous injection of paramagnetic contrast material (Fig. 9–19).

Angioimmunoblastic lymphadenopathy is a proliferative disease of the lymphoid system from which a malignant lymphoma may arise and for which the etiology is unknown. Matthews et al112 reported the case of a patient with this condition who developed a retrobulbar optic neuropathy from infiltration of the nerve by lymphoma cells.

Multiple myeloma, lymphomatoid granulomatosis, and Langerhans cell histiocytosis can all produce an optic neuropathy.109,124–128 In some of these cases, the

optic neuropathy, which may be of the anterior or retrobulbar variety, appears to be produced by infiltration of the nerve129 rather than from compression.130,131 Leukemia is a well-described cause of infiltrative optic neuropathy.132–141

In some of the patients, visual acuity is lost abruptly, whereas in others, there is a gradual progression of visual loss over days, weeks, or months. In still others, the disc appears swollen, but there is no evidence of visual dysfunction. Most patients with leukemic infiltration of the optic nerve are known to have leukemia at the time the visual loss occurs or the patient is found to have asymptomatic disc swelling; however, in some cases, as occurs in patients with lym-

phomatous infiltration of the optic nerve (see previous discussion), the optic neuropathy is the first evidence of the disease.133,142

There appear to be two distinct clinical patterns of optic nerve infiltration by leukemia: (a) infiltration of the optic disc and (b) infiltration of the immediate retrolaminar portion of the proximal optic nerve. In leukemic infiltration of the

optic disc, the features of the disc are obscured by a whitish fluffy infiltrate that is often associated with true disc swelling and peripapillary hemorrhage143,144