Case Reports

Childhood Optic Nerve Glioma:
Vision Loss Due to Biopsy
Karen E. Revere, M.D.*†‡, William R. Katowitz, M.D.*†‡,
James A. Katowitz, M.D.*†‡, Lucy Rorke-Adams, M.D.‡§,
Michael J. Fisher, M.D.‡║, and Grant T. Liu, M.D.*†‡
Abstract: Two children without neurofibromatosis type
1 presented with unilateral decreased vision and MRI
revealing optic nerve tumors. In the first case, chemotherapy
was initiated empirically for presumed optic pathway glioma,
but the lesion increased in size with associated clinical
worsening, raising concern for a possible alternate diagnosis.
Biopsy of the involved optic nerve resulted in worsening of
vision due to a branch retinal artery occlusion and showed
a grade I pilocytic astrocytoma. In the second case, sudden
symptom onset and rapid tumor growth prompted an optic
nerve biopsy, resulting in vision loss due to a central retinal
artery occlusion and revealing grade I pilocytic astrocytoma.
In both cases, tissue diagnosis did not alter the course of
management. Instead, biopsy was associated with additional
vision loss, highlighting the risk of biopsy in children
with isolated optic nerve tumors and imaging that is most
consistent with an optic pathway glioma.
There was no family history of NF1, and he did not have any
stigmata of NF1. His best-corrected visual acuity (VA) was
20/20 OD and 20/50 OS. He saw 6/15 Ishihara color plates OD
and 4/15 OS. He had a sluggishly reactive left pupil and a left
relative afferent pupillary defect. Humphrey visual field testing
showed a left superotemporal defect. External and anterior seg-
ment examinations were normal. On dilated examination, the
right optic nerve was normal, but the left optic nerve was swol-
len and slightly pale.
An orbital MRI revealed an ovoid, T2 hyperintense and
homogeneously enhancing lesion in the left orbit, seemingly
within the optic nerve sheath, that was thought to represent a
schwannoma, meningioma, or optic nerve glioma (Fig. A).
After a discussion between the neuro-radiologist and the clini-
cal team, it was felt that the lesion was most consistent with an
optic nerve glioma. Given his new vision loss, a 10-week course
of induction chemotherapy with carboplatin and vincristine was
initiated. On follow-up examination, his vision was stable OS,
but Humphrey visual field showed an enlarged superotemporal
visual field deficit. Repeat orbital MRI revealed a small interval
increase in tumor size and new involvement of the intracana-
licular portion of the left optic nerve. Given the initially broad
differential diagnosis and increase in lesion size with associ-
ated clinical worsening despite the standard OPG chemotherapy
regimen, a biopsy was requested for definitive diagnosis and

O ptic pathway gliomas (OPGs) are primarily pediatric

tumors of the visual pathway that are often associated with
neurofibromatosis type 1 (NF1). Other entities that can involve
the optic nerve in children include meningiomas, schwannomas,
and inflammatory conditions. Most OPGs in children are World
Health Organization grade I pilocytic astrocytomas.1 Although
rare, some children may develop higher-grade gliomas with
malignant histopathologic features.2 An exact incidence of each
tumor type is not available because biopsies are infrequently per-
formed. Instead, characteristic neuroimaging and clinical exam
findings are used to guide management.1 Although uncommon,
biopsy may be performed in patients with tumors involving the
optic nerve who do not have NF1 and display atypical clini-
cal or radiographic features. Here, the authors report 2 children
with non-NF1-associated optic nerve tumors in whom biop-
sies were pursued. In both cases, pathology revealed pilocytic
astrocytoma, but biopsy resulted in permanent additional vision
loss, calling into question the utility of biopsy in these clinical
situations.
This study was conducted in accordance with the pro-
visions of the Declaration of Helsinki and in compliance with
the Health Insurance Portability and Accountability Act. The
authors do not have any conflicts of interest.
CASE 1
A previously healthy 15-year-old boy was referred for
evaluation of a mass involving the left optic nerve. He reported
a decrease of vision in the left eye 6 months before presentation.
treatment guidance. Incisional biopsy was performed through
a lateral orbitotomy approach via a lateral canthotomy incision.
Pathology revealed a low-grade pilocytic astrocytoma.
Immediately postoperatively, his VA had decreased to
20/125 OS, and a complete left superior altitudinal defect and
a left inferior branch retinal artery occlusion were found. Oral
steroids were administered without improvement. His chemo-
therapeutic regimen was changed to bevacizumab and irinote-
can, which was continued for 1 year with improvement in VA to
his prebiopsy baseline of 20/50 OS. However, there was persis-
tence of the left superior altitudinal visual field defect. The OPG
remained stable in size without further radiographic involve-
ment of the chiasm.
CASE 2
A previously healthy 10-year-old girl was admitted for
acute onset proptosis and several days of blurred vision in the
right eye. There was no family history of NF1, and she did not
have any stigmata of NF1. Her VA was 20/125 OD and 20/20
OS. She had full visual fields by confrontation. External and
anterior segment examinations were normal. Dilated examina-
tion was notable for right optic nerve swelling with peripapillary
hemorrhages. Orbital MRI revealed an enhancing intraconal, T2
hyperintense and heterogeneous mass in the right orbit, seem-
ingly within the optic nerve sheath (Fig. B). In contrast to case

*Department of Ophthalmology, Scheie Eye Institute, †Division of

Ophthalmology, The Children’s Hospital of Philadelphia, ‡Perelman School
of Medicine at the University of Pennsylvania, §Division of Pathology,
The Children’s Hospital of Philadelphia, and ║Division of Oncology, The
Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, U.S.A.
Accepted for publication February 5, 2016.
The authors have no financial or conflicts of interest to disclose.
Address correspondence and reprint requests to Karen E. Revere, M.D.,
Division of Ophthalmology, Children’s Hospital of Philadelphia, 34th and
Civic Center Blvd., Philadelphia, PA 19104. E-mail: reverek@email.chop.edu
DOI: 10.1097/IOP.0000000000000687
A, Case 1: T1-weighted, postgadolinium, axial MRI image
showing a left orbital enhancing lesion (arrow) within the optic
nerve sheath with extension from the optic disc to just anterior
to the optic canal. B, Case 2: T1-weighted, postgadolinium axial
MRI image showing a right enhancing orbital mass, within the
optic nerve sheath (arrow) with indention of the posterior globe
and extension to the orbital apex.

Ophthal Plast Reconstr Surg, Vol. XX, No. XX, 2016 1

Copyright © 2016 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. Unauthorized reproduction of this article is prohibited.
 Case Reports Ophthal Plast Reconstr Surg, Vol. XX, No. XX, 2016
1, she presented with rapid symptom onset and tumor growth
that raised concern for a more aggressive tumor type, such as
rhabdomyosarcoma, and a biopsy was requested for definitive
diagnosis. Incisional biopsy was performed through a right
anterior orbitotomy approach via a lateral canthotomy incision.
Pathology revealed a low-grade pilocytic astrocytoma.
Postoperatively, her vision had decreased to no light per-
ception in the right eye, with a nonreactive right pupil and right
afferent pupillary defect. A right central retinal artery occlusion
was found, but concurrent worsening of the optic neuropathy
was felt to be responsible for no light perception vision. Vision
did not improve with a course of oral steroids. Over the next
year, she received chemotherapy with vincristine and carbopla-
tin. The lesion continued to fluctuate in size, but never extended
into the chiasm or contralateral visual pathway. Two years after
diagnosis, a hemorrhage occurred within the tumor, causing
increased proptosis. Given no light perception vision and disfig-
urement, debulking of the intraorbital right optic nerve was per-
formed, and pathology was the same as that of the initial biopsy,
showing a low-grade pilocytic astrocytoma.
Optic pathway gliomas are intrinsic to the structures of
the visual pathway and are therefore infrequently biopsied due to
risk of vision loss. The diagnosis of OPGs in children is almost
exclusively based on imaging in patients with NF1. In non-NF1
patients, biopsy of tumors of the optic pathway is sometimes con-
sidered for those without classic imaging findings, particularly
for lesions posterior to the optic chiasm.3 Excisional and inci-
sional biopsies of optic nerve lesions are generally performed in
the setting of severe vision loss or absent vision (where the risk
of biopsy is minimal given already very poor vision), painful
or disfiguring proptosis, or when vision to the contralateral eye
is threatened.4 There are variable complication rates described
from incisional optic nerve biopsy. In the few reported cases
where vision was not affected postoperatively, most biopsies
were inconclusive, possibly suggesting that a portion of the
intrinsic optic nerve fibers were not adequately sampled.4,5
Here, the authors describe 2 children with sporadic optic
nerve tumors in whom biopsies were performed. Neither child
had NF1, and both were older than the typical age of onset for
sporadic OPGs, which may have also contributed to uncer-
tainty about lesion diagnosis.1 There was also some radiologic
ambiguity about lesion appearance in both cases. Despite the
atypical nature of each child’s tumor, histopathology revealed
low-grade pilocytic astrocytoma. Furthermore, in both cases,
vision decreased postoperatively from retinal artery occlusions,
which the authors hypothesize occurred from optic nerve trac-
tion and/or contusion during intraoperative manipulation. In the
first case, VA returned to baseline, but a dense residual superior
visual field defect remained. In the second case, VA decreased
irreversibly, and the lesion continued to fluctuate in size, even in
the setting of confirmed low-grade histology.
Although there are no standardized guidelines, the main
indications to initiate therapy in NF1 OPGs are a decline in
vision and/or tumor progression. Chemotherapy (particularly
carboplatin-based regimens) is usually used first line due to the
risks associated with surgical resection and radiotherapy.6 In
non-NF1 OPGs, chemotherapy is more likely to be started at the
time of diagnosis, as these tumors behave differently than NF1
tumors. Sporadic OPGs are more commonly associated with
vision loss at the time of diagnosis and less likely to remain
stable in size over time.7,8
2 © 2016 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.
Copyright © 2016 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. Unauthorized reproduction of this article is prohibited.
There are few studies in the literature that adequately
assess VA outcomes after chemotherapy, but a large retrospec-
tive series in patients with NF1 OPGs showed improvement or
stability of vision in the majority of those treated.9 However,
a fraction of patients had worsening of vision despite che-
motherapy, which may be reflective of damage occurring
before the initiation of therapy or from frank tumor progres-
sion.9 While the authors feel that VA is a better measure of
response to therapy than tumor size, vision response may not
always correlate with tumor response to chemotherapy.3,9,10
Furthermore, there is recent evidence that a large percentage
of NF1 and non-NF1 OPGs may not be responsive to first-
line chemotherapeutic regimens and may eventually require a
second-line agent.8,11
These are only 2 cases, but they demonstrate the poten-
tial morbidity associated with optic nerve biopsy. In each case,
biopsy revealed World Health Organization grade I pilocytic
astrocytoma, but resulted in permanent vision loss without sig-
nificantly altering the course of treatment. Given the high preva-
lence of OPG in NF1, biopsy is almost never recommended.
However, in non-NF1, biopsy may be requested if there is diag-
nostic uncertainty. These cases highlight the potential risks of
this approach and suggest that biopsy of optic nerve tumors
with at least some features of an optic nerve glioma should be
pursued with more caution in non-NF1 children who may have
tumor progression and/or worsening of vision despite standard
chemotherapy regimens.
REFERENCES
1. Avery RA, Fisher MJ, Liu GT. Optic pathway gliomas.
J Neuroophthalmol 2011;31:269–78.
2. Louis D, Ohgaki H, Wiestler O, et al. WHO Classification of
Tumours of the Central Nervous System. Lyon, France: IARC Press;
2007.
3. Campagna M, Opocher E, Viscardi E, et al. Optic pathway glioma:
long-term visual outcome in children without neurofibromatosis
type-1. Pediatr Blood Cancer 2010;55:1083–8.
4. Levin MH, Ney JJ, Venneti S, et al. Optic nerve biopsy in the
management of progressive optic neuropathy. J Neuroophthalmol
2012;32:313–20.
5. Khong JJ, McNab AA. Medial transconjunctival intrinsic optic nerve
biopsy: surgical technique and indications. Orbit 2012;31:227–32.
6. Ater J, Holmes E, Zhou T, et al. Abstracts from the thirteenth inter-
national symposium on pediatric neuro-oncology: results of COG
protocol A9952-a randomized phase 3 study of two chemotherapy
regimens for incompletely resected low-grade glioma in young
children. 2001;23:349–52.
7. Chateil JF, Soussotte C, Pédespan JM, et al. MRI and clinical differ-
ences between optic pathway tumours in children with and without
neurofibromatosis. Br J Radiol 2001;74:24–31.
8. Shofty B, Mauda-Havakuk M, Weizman L, et al. The effect of che-
motherapy on optic pathway gliomas and their sub-components:
a volumetric MR analysis study. Pediatric Blood and Cancer
2015;62:1353–1359.
9. Fisher MJ, Loguidice M, Gutmann DH, et al. Visual outcomes in
children with neurofibromatosis type 1-associated optic pathway
glioma following chemotherapy: a multicenter retrospective analy-
sis. Neuro Oncol 2012;14:790–7.
10. Opocher E, Kremer LC, Da Dalt L, et al. Prognostic factors for pro-
gression of childhood optic pathway glioma: a systematic review.
Eur J Cancer 2006;42:1807–16.
11. Shofty B, Ben-Sira L, Freedman S, et al. Visual outcome follow-
ing chemotherapy for progressive optic pathway gliomas. Pediatr
Blood Cancer 2011;57:481–5.