34.4 Intraorbital Optic Nerve Glioma

34.4.1 Description and Clinical Issues

The term intraorbital optic nerve glioma refers to tumors of the optic nerve and includes juvenile pilocytic astrocytoma of the optic nerve proper. A number of optic nerve growths in NF1 patients are very stable and cause no visual loss; it is thought that many of these growths are actually dural ectasia (thickening of the optic nerve sheath) and are not really a dividing tumor. True optic nerve gliomas occur as early as the first year of life, and the incidence peaks between 4 and 6 years of age [7]. These tumors rarely progress if they are still asymptomatic when a patient reaches 6 years of age. As a group, these tumors all appear on MRI as abnormal thickening of the orbital component of the optic nerve.

Optic nerve gliomas may be detected because of the presence of proptosis, disorder of extraocular movement, visual loss, optic disc swelling and/or pallor, or asymptomatic incidental findings on MRI.

It is important to determine whether optic nerve gliomas are growing or stable. As mentioned above, many cases of optic nerve glioma are thought to represent simple dural ectasia, an asymptomatic lesion that does not affect the patient’s vision and extraocular motility, representing an incidental finding on screening MRI or CT. Dural ectasias are nonprogressive and should not be treated. Some believe that the optic nerve glioma in NF1 is really a hamartoma. Some clinicians conclude that only symptomatic tumors actually require attention and that MRI of the orbit in patients with NF1 is indicated only in cases of disturbance of visual acuity or extraocular motility. This position has been formalized in some published principles of management for NF1 patients [6]. A second school of thought suggests that early detection leads to closer scrutiny of visual status in the affected child, making routine MRI for all children with NF1 more prudent. An additional argument in favor of MRI screening is that clinically silent features of NF1, such as glioma of the optic chiasm, hypothalamus, or other areas, may be detected as part of the screening process. Given the varying approaches to MRI screening, the exact ratio of asymptomatic to symptomatic tumors is unknown, but it is estimated to be about 10:1.

Many cases of symptomatic optic nerve glioma are histopathologically proven juvenile pilocytic astrocytoma. These cases are identified from tissue samples obtained during debulking of symptomatic mass lesions. The mechanism of visual loss is presumed to be invasion of the central core of the optic nerve with subsequent disruption of the axon bundles comprising the optic nerve. The slowly progressive nature of the visual loss caused by these tumors supports this idea. Proptosis— due to a dense mass effect of the thickened optic nerve or cystic accumulations of spinal fluid along the optic nerve—is present in some but not all cases of symptomatic intraorbital optic nerve glioma. Of note, a number of these gliomas actually involve the entire visual pathway, including the intracranial optic nerve, chiasm, and tract.

34.4.2 Evaluation and Management

Asymptomatic intraorbital optic nerve gliomas are generally diagnosed by a screening MRI; at the time of discovery, the tumors should be considered presymptomatic until proven otherwise. No specific protocol exists for clinical follow-up or routine imaging. A strong case can be made for yearly follow-up MRIs until the age of 6 years, accompanied by careful ophthalmologic examination every 6 months, then yearly thereafter. Formal visual field testing is perhaps the most sensitive and reproducible tool for measurement of visual impairment, but the early age of onset, e.g., 18–24 months, makes this approach untenable. Some children can do visual field testing reliably at age 3, but most cannot. Because many children with NF1 also have attention-deficit disorder, visual field testing may be unreliable even at older ages. Regular visual evoked response testing has been endorsed by some authors, but the utility of this procedure remains untested in large clinical trials [11]. We endorse careful ophthalmologic examination with attention to vision and visual function, confrontation visual field testing, and a careful pupil examination with quantification of afferent pupillary defects when possible.

Management options for optic glioma disorders depend on the loss of visual function and/or the development of proptosis. Some children with optic nerve gliomas develop a sensory esotropia or exotropia, and a component of the visual loss may be from amblyopia; however, in our experience, if there is a deviation of the eye from an optic nerve glioma, most of the visual loss is from the optic nerve problem and not due to the strabismus causing amblyopia. However, it is not unreasonable to try patching of the good eye to see if there is improvement in the eye with the optic glioma and strabismus. Management of progressive and severe proptosis may include surgical debulking, but this approach will not likely improve visual function.

Chemotherapy can be considered if possible, and radiation therapy should be considered as a last resort. Chemotherapy for optic nerve glioma has been studied in a trial at the Children’s Cancer Group (CCG A9952). This trial included a comparison of response rates of optic nerve glioma in children with and without NF1. The response rate for the two clinical groups was similar and, to date, combination of cisplatin and vincristine remains the most commonly used regimen. The trial results are not formally available; however, the response rates were reportedly up to 50%. However, treatment of these benign-acting tumors still remains controversial, in that we do not know whether the natural history of vision loss with or without treatment is better. Also there are documented cases where vision improves without intervention.

Radiation therapy remains a highly controversial modality for patients with NF1. Although radiation produces excellent control in over 90% of patients, long-term secondary effects do occur, including secondary tumors and radiation injury to the optic nerve itself [12, 13]. Some reports indicate that the long-term outcome for vision may be improved following radiation treatment [14]. In the Children’s Cancer Group trial, children with NF1 below the age of 2 years were not allowed to receive radiation therapy because of the general risk of radiation injury to the developing