Optic Nerve Glioma

A low grade glioma (pilocytic astrocytoma in most) of the optic nerve, chiasm, optic tracts and radiations. It accounts for about 2 to 5 percent of childhood brain tumours.

• Occurs mainly in children aged 2 to 8 years (peak around 4 to 5); about 20 to 50 percent of cases are associated with neurofibromatosis type 1 (NF1), in which tumours are often bilateral and tend to be indolent. Sporadic tumours are usually unilateral and more progressive.
• In older adults, malignant optic glioma (glioblastoma of the anterior visual pathway) is rare and rapidly fatal.
• Molecular: BRAF alterations (KIAA1549-BRAF fusion) in sporadic tumours; loss of NF1 gene function in neurofibromatosis.

• Slowly progressive painless visual loss (variable, can be absent), axial proptosis, relative afferent pupillary defect, optic atrophy or disc swelling, strabismus, nystagmus (seesaw type with chiasmal lesions, spasmus nutans like in infants).
• Chiasmal and hypothalamic extension: visual field loss (bitemporal), endocrine abnormalities (precocious puberty, growth hormone deficiency), diencephalic syndrome (failure to thrive with emaciation despite normal intake, euphoria), hydrocephalus and headache.
• NF1 features: café-au-lait macules (6 or more over 5 mm), axillary freckling, Lisch nodules, neurofibromas.
• Visual outcomes vary: stable in many NF1 cases, with growth in about 20 to 30 percent.

• MRI orbits and brain with gadolinium: fusiform enlargement of the optic nerve with tortuosity or kinking, enhancement, perineural arachnoid gliomatosis, extension along tracts. Diagnosis is by imaging; biopsy is not needed for typical NF1-associated lesions.
• Biopsy for atypical imaging or rapid progression without NF1.
• Ophthalmic assessment: visual acuity (preferential looking in infants), colour vision, pupils, fields, optical coherence tomography (retinal nerve fibre layer thickness), visual evoked potentials.
• Clinical examination and genetic testing for NF1; endocrine testing (growth, puberty, IGF-1, thyroid, cortisol) for chiasmal or hypothalamic involvement.
• Monitoring MRI every 3 to 6 months initially, then yearly if stable.

• Observation for stable asymptomatic or NF1-associated tumours with MRI and visual assessment every 3 to 6 months.
• Indications for treatment: documented visual decline, tumour growth, hypothalamic involvement, progressive proptosis, endocrine problems.
• Chemotherapy first line: carboplatin 175 mg/m2 IV weekly for 4 weeks followed by 2 weeks of rest (induction 10 weeks), with vincristine 1.5 mg/m2 weekly for 10 weeks, then maintenance for 8 cycles at 3 to 4 weekly intervals; alternatives: vinblastine 6 mg/m2 weekly, carboplatin alone, temozolomide, or bevacizumab 10 mg/kg every 2 weeks with irinotecan.
• Targeted therapy: MEK inhibitors (selumetinib 25 mg/m2 orally twice daily in NF1 low grade gliomas, trametinib 0.025 mg/kg daily, with dabrafenib for BRAF V600E tumours); monitor for rash, cardiomyopathy, retinopathy and elevated creatine phosphokinase.
• Radiotherapy (50 to 54 Gy) is avoided in NF1 and young children because of cerebrovascular disease (moyamoya), endocrine problems, cognitive impairment and secondary tumours; proton beam is reserved for older children with sporadic tumours when chemotherapy fails.
• Surgery: resection of a blind, disfiguring orbital tumour (isolated nerve glioma with proptosis) with a long section of nerve; hydrocephalus shunting; avoid debulking chiasmal tumours.
• Amblyopia therapy (patching) in the contralateral eye, low vision aids, endocrine replacement (growth hormone, gonadotropin releasing hormone agonists for precocious puberty, hydrocortisone, levothyroxine), and neuropsychological support.