Optic nerve gliomas are rare, comprising 1% of all intracranial tumors; but 4-6% of all brain tumors in children. Eighty-five percent occur in children under 15 years of age and the female/male ratio is 3:2.  

Pathology:

About 10 per cent of optic pathway tumors are located within an optic nerve. One third of the tumors involve both optic nerve and chiasm, a further third involve predominantly the chiasm itself, and one fourth are predominantly in the hypothalamus.5 5% are multicentric.  

Although it has previously been suggested that these lesions are hamartomas, most authorities now accept that they are truly neoplastic. These tumors are usually slow-growing low grade (pilocytic) gliomas. Occasionally malignant ones also found at this location usually in adults. Rarely, a malignant optic glioma can occur in a child. In childhood, the optic pathway tumors are low-grade astrocytomas and rarely gangliogliomas. However, optic pathway gliomas can occur in adults, and in that situation the tumors may have the characteristics of a highly malignant tumor that causes early loss of vision and inevitably leads to the patient's death.

Macroscopically, these tumors may be solid, gelatinous or cystic. Although having certain gross similarities with oligodendrocytes, closer microscopic, ultrastructural and immunostaining techniques have confirmed their low grade astrocytic (pilocytic) nature with the presence of numerous Rosenthal’s fibres. The tumor may start in the anterior end of the optic nerve and proceed backwards intracranially or may arise originally from the optic nerve-chiasma junction. Occasionally, a glioma from the optic tract or the anterior third ventricle region may involve the chiasma and the optic nerve secondarily.  About 40 per cent of optic pathway astrocytomas are fibrillary and 60 per cent are pilocytic. Hypothalamic tumors which have invaded the optic chiasm behave differently, showing evidence of local invasion and histologically are not pilocytic in nature but are similar to other cerebral hemisphere gliomas.

About one third of the patients with optic pathway hypothalamic gliomas will have neurofibromatosis type1. Patients with neurofibromatosis have histologically similar tumors but the tumors are more likely to be associated with extensive arachnoidal hyperplasia and florid local gliomatous infiltration of the leptomeninges. Indeed, in NF-1 patients optic nerve lesions may be due to diffuse hyperplasitc gliosis rather than actual neoplasia. Multicentric tumors involving both optic nerves are also usually associated with NF-1.

Clinical features:

The evolution of symptoms is slow and insidious and depends on the site of origin. In general, optic nerve tumors present at a slightly later age (6 years) than the hypothalamic/chiasmatic tumors (2 to 4 years).

Tumors restricted to optic nerve produce failing vision in one eye. It is often not detected by children for a long time. Papilledema (probably due to venous obstruction), being more common than optic atrophy is the cause for visual failure. Proptosis is delayed. Optic atrophy in a child with no retinal or macular degeneration points to an optic nerve glioma, especially in neurofibromatosis. 20-30% of the patients have café-au-lait spots. Irregular visual field defect is diagnostic. Initially there is central or paracentral scotoma.

Tumors that involve the chiasma produce bilateral irregular visual field defect. The loss of visual acuity is secondary to optic atrophy.

Unfortunately posteriorly located tumors are the most common form of optic nerve gliomas (60%) and it is often difficult to determine the actual origin of the tumor as they are frequently large and involve both the chiasm and the hypothalamus. Patients may present with hydrocephalus (due to obstruction of the foramen of Monro), visual problems (acuity and field defects), pituitary dysfunction or hypothalamic dysfunction. The latter, classically leading to the diencephalic syndrome (emaciation, pallor, and hyperactivity), is seen in up to 20% of patients under 3 years of age. When the hypothalamus is involved, particularly in infancy, the child may present with a diencephalic syndrome.³ Other symptoms of hypothalamic involvement include diabetes insipidus, anorexia, obesity and precocious puberty.

Differential diagnosis:

Optic nerve glioma

             Hemangioma, Lymphoma, Rhabdomyosarcoma, Metastases (Neuroblastoma,

             Leukamia, Ewing’s sarcoma), Fibrous dysplasia,  Paranasal mucocoele, Meningioma, Neurofibromatosis

            (Orbital neurofibroma, Congenital defect in sphenoid bone)

Optic nerve and chiasm glioma

            Germinoma,  Sarcoidosis

Optic chiasm glioma extending into the hypothalamus

            Pituitary adenoma, Craniopharyngioma, Malignant astrocytoma, Epidermoid

            and dermoids, Chordoma, Colloid cyst, Fibrous dyplasia, Sarcoidosis, Histiocytosis X

            Tuberculous granuloma, Hemangloendothelioma.

MRI is far more sensitive for displaying chiasmatic/hypothalamic tumors than CT. These tumors are usually hypointense on T1-weighted images and hyperintense on T2 and almost always, enhance with gadolinium. On T2, high intensity signal may be seen extending to the lateral geniculate bodies.

When the tumor involves the chiasm and the hypothalamus, it can reach an enormous size, particularly in infancy. In such situations there is often extensive distention of the basal cisterns, which can rupture, giving rise to large subdural hygromas that can envelop both cerebral hemispheres.

Visual evoked responses may be of assistance in monitoring visual function; but it is of limited value. 

Management:

They are usually slow growing and very occasionally may become malignant and grow rapidly. Ten year survival rates also depend on site and range from 76% to 95% for posteriorly and anteriorly situated pilocytic tumors respectively. The treatment remains controversial and is dependent upon the site of the tumor especially when the optic chiasm and/or the hypothalamus is involved, and ranges from observation alone to operative intervention with or without adjuvant therapy. Some physicians advocate resection without any further therapy, others recommend radiation therapy or chemotherapy, and still others believe that no therapy is required.

The natural history of this tumor is variable and spontaneous regression can occur. This should be kept in mind in deciding on treatment. Patients with an optic glioma and neurofibromatosis type 1 have a better prognosis than those who do not have neurofibromatosis.

Orbital and Intracranial optic nerve tumors: Not infrequently, asymptomatic optic nerve tumors are detected whilst imaging patients with neurofibromatosis. In those patients with reasonable and/or static visual acuity, surveillance with regular ophthalmological assessment and imaging may be appropriate. 

The aim of surgical treatment is to remove the tumor before there has been spread to the optic chiasm or contralateral optic nerve and to deal with the associated proptosis. Although in patients with orbital optic nerve tumors this may be achieved with relatively little morbidity via an extracranial resection (transorbital approach), the risk of leaving tumor in the optic nerve stump has resulted in most surgeons treating these lesions in the same fashion as those that involve the intracranial optic nerve – with excision of the optic nerve just distal to the optic chiasm to avoid sectioning through the looping fibers of Willbrand.  Patients with an optic glioma and neurofibromatosis type 1 have a better prognosis than those who do not have neurofibromatosis. An orbital glioma can be removed in two pieces. The intracranial optic nerve is removed from in front of the chiasm to the optic canal, and the orbital glioma is removed from the globe to the optic canal. The residual intracanalicular tumor is then coagulated. By doing this there is no need to section the annulus or to divide the origin of the levator and possibly damage the trochlear nerve. 

Optic nerve and chiasmatic tumors: The number of patients reported in the literature is small; it would appear that long-term survival should be expected in this group. Surgery is reserved for diagnostic purposes or to excise an exophytic component: adjunctive therapy is reserved for tumor progression.  

Chiasmatic/hypothalamic tumors: These tumors show markedly varying capacity for progression with some remaining indolent while others rapidly increase in size. Operative debulking of the tumor mass with or without adjuvant therapy is utilized in cases of tumor progression. Although long-term survival has been reported with these tumors, this is usually accompanied by significant morbidity. CSF diversion is frequently required.

In patients without visual compromise with large tumors filling the third ventricle, a transcallosal approach to the tumor using a subchoroidal approach to the third ventricle has been a very useful technique for removing large volumes of tumor. In some cases the biological effect of resecting these tumors can lead to its stabilization or even involution and occasionally to complete disappearance. Patients with an optic glioma and neurofibromatosis type 1 have a better prognosis than those who do not have neurofibromatosis.

Adjuvant therapy:

The role of adjuvant therapy in the treatment of optic pathway tumors remains controversial. The young age of the patients considerably limits the use of radiotherapy but none the less, for posterior tumors, irradiation may be effective in adults with a 75% 10 year relapse-free survival. Side-effects of radiation therapy include endocrine dysfunction, secondary malignancy and an increased risk of developing moyamoya phenomenon especially in the setting of NF-1. This is particularly true in children younger than 5 years of age. Patients with an optic glioma and neurofibromatosis type 1 have a better prognosis than those who do not have neurofibromatosis.

Of the chemotherapeutic agents available, the nitrosourea-based cytotoxic regiments have been shown to result in symptomatic improvement or stabilization. Certainly, there is a role for chemotherapy in those patients with progressive disease who are too young to receive radiotherapy. Good outcome have been reported with chemotherapy. Patients with an optic glioma and neurofibromatosis type 1 have a better prognosis than those who do not have neurofibromatosis. More recently, carboplatin has been reported to be effective in arresting growth in progressive optic gliomas but a larger trial is required to substantiate this.