How Should a Childhood Optic Nerve Glioma Be Worked Up?
An 8-year-old boy presents with vision of 20/40 right eye (OD) and 20/20 left eye (OS). He has a right relative afferent pupillary defect (RAPD) and a pale optic nerve OD. The left fundus is normal. Magnetic resonance imaging (MRI) findings are consistent with a right optic nerve glioma. How should this patient be evaluated?
Let us be frank. There are no treatments with demonstrated effectiveness in curing optic gliomas or preventing the vision loss that may be associated with them. Thus, the main management decision is determining if and when the various unproven and in some cases even somewhat “experimental” therapy should be started. This decision depends on understanding the prognosis for untreated optic nerve gliomas, which in turn, depends on the age of the patient and whether or not he or she is afflicted with neurofibromatosis type 1 (NF-1).
In general, patients with NF-1 have a better visual prognosis and their optic nerve gliomas rarely cause progressive vision loss beyond the age of 12. An assessment of afflicted children for café-au-lait spots, Lisch nodules, and family history of possible NF-1 is essential. Genotyping is rarely necessary but is available and should be discussed with a geneticist. You should be more reluctant to pull the treatment trigger on a patient with NF-1, since the untreated prognosis is relatively good, and since there is a theoretical risk of inducing tumors elsewhere in patients with a mutation of a growth control gene. This is of particular concern if your oncologist is considering radiation therapy.
Regardless of whether or not the afflicted patient has NF-1, I believe that no treatment should be started without documented progression of vision loss or hypothalamic dysfunction. The fact that the patient presents with diminished vision is not sufficient. The diminished vision may have been stable for years, even for life. It is also not sufficient for a single decrement in visual acuity from one exam to the next to be considered progressive vision loss. Many patients have fluctuating vision or full recovery of vision regardless of whether or not the tumor is changing in size on the MRI scan. Consequently, there should be some documentation of progressive vision loss over at least 2 to 3 examinations and the vision loss should be approaching the threshold for a change in functional significance (eg, losing reading ability or independent mobility).
Since your particular patient is 8 years old and literate age, you have many monitoring tools at your disposal to help in your decision as to when to refer for chemotherapy. Besides measuring best-corrected visual acuity, you can monitor visual fields. This is best done with Goldmann perimetry, since it is more reliable than automated perimetry at this age and since the examiner can focus on those areas of known field loss before the patient’s attention is lost. You should also consider monitoring color vision. I would not base treatment decisions on color vision, but an isolated drop in color vision would cause me to increase the examination frequency. Finally, baseline optic disc photos and/or optical coherence tomography should be obtained and repeated for confirmation if there is suspicion of worsening optic atrophy.
How often should you follow this patient? In general, the frequency of visits depends on the stability of the examination and the age of the patient. The longer you follow a patient with a stable ophthalmic examination, the less frequent need be the visits. I will usually see an 8-year-old patient 2 to 3 months following the first examination, then semi-annually for 2 to 3 years, then annually. I will follow children who present at less than
3 years of age more frequently.
The role of repeat neuroimaging is controversial. I generally do not find it useful in making treatment decisions unless I suspect nonophthalmic consequences of tumor enlargement, such as hypopituitarism or impending hydrocephalus. Nonetheless, parents seem to find comfort in documenting neuroradiographic stability or even shrinkage. Spontaneous regression of optic gliomas with or without improvement in vision has also been documented on serial MRI scans.
As I previously mentioned, the treatment options are limited. Most neuro-oncologists will treat with some combination of chemotherapy that includes vincristine, carboplatin, and/or temozolomide. The side effects of these medications are similar to, but generally less severe than, those used to treat most childhood malignancies. These agents are believed to arrest progression and, in some cases, cause tumor regression based on MRI. No controlled studies and no studies using vision outcomes have been done.
Surgical excision of unilateral optic gliomas has been advocated in some cases to prevent progression to chiasm involvement or to relieve unsightly exophthalmos. Obviously, this treatment causes blindness, so it should probably be reserved for patients with severely impaired vision. The effectiveness of surgical excision is controversial. There is no evidence that optic gliomas actually spread to uninvolved parts of the visual pathways. There have been numerous documented cases of histological involvement of the chiasm despite the fact that the tumor appeared confined to the orbit on MRI scan.
Radiation therapy results in tumor shrinkage but can also cause worsening vision loss. It should best be avoided if possible in very young children because of the concomitant risk of cognitive impairment and hypothalamic injury.
Fortunately, progressive vision loss and nonophthalmic complications are the exception, rather than the rule, in cases such as these. In my experience, parents are relieved to hear this and can accept expectant observation as a management option over immediate treatment once the facts about optic gliomas and their treatment are calmly explained.
* Optic nerve glioma is typically a tumor of childhood.
* Some patients have NF-1.
* No treatment has been proven to be effective.
* Observation for clinical or radiographic stability or progression is the first line of management.
* Chemotherapy and radiation therapy have been used in selected patients with progressive disease but is unproven.
* Surgical excision of an optic nerve glioma has a limited role for patients with blind eyes with cosmetically unacceptable proptosis.
Hwang JM, Cheon JE, Wang KC. Visual prognosis of optic glioma. Childs Nerv Syst. 2008; PMID 18175125.
Parsa CF, Hoyt CS, Lesser RL, et al. Spontaneous regression of optic gliomas: thirteen cases documented by serial neuroimaging. Arch Ophthalmol. 2001;119:516-529.