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Childs Nerv Syst

DOI 10.1007/s00381-017-3578-8


Optical coherence tomography as a marker of vision

in children with optic pathway gliomas
Ana Banc 1 & Cristina Stan 1,2 & Ioan Stefan Florian 3,4

Received: 21 October 2016 / Accepted: 16 August 2017

# Springer-Verlag GmbH Germany 2017

Abstract Keywords Optic pathway glioma . Children . Optical

Purpose Optic pathway gliomas (OPG) represent an impor- coherence tomography . Retinal nerve fiber layer . Review
tant cause of visual loss in pediatric population. The indication
of treatment is based on clinical or neuroimaging progression.
Visual acuity loss is the most important symptom of disease
progression, but children with OPG are frequently unable to Introduction
complete the testing of visual function. Optical coherence to-
mography (OCT) was suggested as an objective tool for visual Optic pathway gliomas (OPG) are low-grade pilocytic astro-
assessment. A literature review was performed in order to cytomas intrinsic to the precortical visual pathway and repre-
determine the role of retinal OCT as a surrogate marker of sent 3–5% of brain tumors in children [8, 33]. Approximately
vision in children with OPG. 65% of OPG are diagnosed before the age of 5 and represent
Methods The search was performed using PubMed, Embase, an important cause of vision loss in pediatric population [33].
and Web of Science databases and was restricted to articles OPG are also detected in 13–20% of patients with neurofibro-
published in English between 2000 and 2016, with a mini- matosis type 1 (NF1), an autosomal dominant disorder with an
mum of ten participants enrolled. incidence of 1:3.500–1:4.000 births [14]. Children with OPG
Results Eleven studies met the eligibility criteria and were require frequent and long-term monitoring for ophthalmolog-
included in the present review. Both neurofibromatosis-1 as- ical abnormalities [31].
sociated and sporadic OPG were investigated. In 1997, the OPG task force established a set of guidelines
Conclusions Retinal OCT is a promising tool to be considered for the diagnosis and treatment of OPG associated to NF1
as a screening or follow-up test in children with OPG, and [32], and the recommendations were revised a decade later
further multicenter research is encouraged. [31]. According to the OPG task force, the indication to initi-
ate treatment is based on clinical or neuroimaging progres-
sion. The main symptom of clinical progression is considered
* Ana Banc the visual acuity loss [31]. However, young children with OPG are frequently unable to complete visual function testing
due to lack of cooperation. This inability is more pronounced
Department of Ophthalmology, Iuliu Hatieganu University of
in children with NF1, who often have developmental delay
Medicine and Pharmacy, Clinicilor Street no 3-5, and attention-deficit disorder [32]. Although the diagnosis of
400006 Cluj-Napoca, Romania OPG is confirmed with neuroimaging and MRI is the exam-
Ophthalmology Clinic, Emergency County Hospital Cluj, ination of choice for monitoring progression or treatment re-
Cluj-Napoca, Romania sponse [13, 31], neuroimaging results were found to be a poor
Department of Neurosurgery, Iuliu Hatieganu University of Medicine predictor of visual outcome [19, 43]. MRI of the brain and
and Pharmacy, Cluj-Napoca, Romania orbits is not recommended as a screening tool in patients with
Neurosurgery Clinic, Emergency County Hospital Cluj, NF1, but it is indicated in cases with documented abnormal
Cluj-Napoca, Romania ophthalmological examination [31, 41].
Childs Nerv Syst

In this context, a surrogate marker of vision is needed in were also investigated in order to establish the level of evi-
order to objectively identify children with visual loss and to dence of each study.
monitor the possible clinical progression. Optical coherence To avoid the bias as much as possible, we established the
tomography (OCT) of the retina has been suggested as such a inclusion and exclusion criteria before performing the search,
tool [15]. OCT is a non-invasive high-resolution imaging and the eligibility evaluation was made by two independent
technique which provides an in vivo optical biopsy of the reviewers based only on inclusion and exclusion criteria. We
retinal layers [20]. OPG may induce damage to the axons of did not use the type of OCT equipment as a criterion for
retinal ganglion cells, which form the retinal nerve fiber layer selecting the studies for the present analysis. We declare no
(RNFL). The RNFL thickness is assessed by OCT and de- conflict of interest for this research.
creased values represent retinal ganglion cell loss, which oc-
curs through Wallerian degeneration if the lesion is located in
the anterior visual pathway and through retrograde trans- Discussion
synaptic degeneration in posterior visual pathway lesions
[28, 29]. OCT proved to be useful in the diagnosis and All the eligible studies had a prospective design, and each was
follow-up of adult patients with tumors of visual pathway conducted in a single institution. Table 1 contains details about
[18, 45]. design of studies, demographic characteristics, and level of
The objective of this review is to determine the role of evidence according to the Oxford Centre for Evidence-
retinal OCT as a potential marker of vision in children with Based Medicine 2011 [26]. All the studies used MRI as refer-
OPG. ence standard test, but the research of Parrozzani et al. [36]
was the only stating both the consecutiveness of patients’
inclusion and blinding for MRI, OCT, and clinical examina-
tion. Gu et al. [23] used blinding only for OCT layer segmen-
Methods tation. All the other articles are lacking information about
inclusion of consecutive patients, or blinding for interpretation
A literature review was performed using the PubMed, of MRI or OCT.
Embase, and Web of Science databases, and it included the
original studies conducted on children diagnosed with OPG, Assessment of visual function in children with OPG
either NF1-associated or sporadic. The search was restricted to
humans, age birth—18 years, and articles published in English Visual decline represents an indication of treatment in children
between 2000 and 2016. A manual search was also performed with OPG. Ophthalmological assessment includes evaluation
in order to identify additional articles. of visual acuity, visual field, color vision, and other neuro-
The preliminary search was based on the following MeSH ophthalmological tests, but visual acuity loss is considered
terms: Boptical coherence tomography,^ Bretinal nerve fiber the most reliable and important clinical symptom of OPG
layer,^ and Boptic pathway glioma.^ Inclusion criteria were [31].
as follows: documented OPG, use of retinal OCT, and a min- Visual acuity assessment is a psychophysical measure and
imum of ten participants enrolled in the study. Exclusion relies on the cooperation and attention of the patient [7]. The
criteria were as follows: associated glaucoma, intraocular tu- examination includes age-adapted visual acuity tests, and dif-
mors, or the presence of other neurological conditions. ferent testing methods are used depending on the child’s age
All the results were screened for relevance by one reviewer and cognitive abilities: preferential looking test is used in in-
(AB) based on title and abstract. The articles considered rele- fants (e.g., Teller acuity test), Lea figure or HOTV matching in
vant were included into full-text assessment, which was per- preliterate children, and Snellen charts in literate children [7,
formed independently by two reviewers (AB, CS). The inclu- 31]. Moreover, normal visual acuities improve with age and
sion and exclusion criteria were used to determine the eligi- different age-related norms must be used in young children
bility of each study. The date of our last search was September [31]. Since the visual acuity of children with OPG is long-term
20, 2016. Eleven articles were assessed in the full-text format, monitored, the same child may complete more complex visual
and none was excluded. acuity tests as his/her cognitive capacity is developed [3, 7].
The following data was collected from the studies: study As the visual acuity scores are not equivalent between the
design, number of participants, demographic characteristics, tests and because there is a great variability in terms of cogni-
tumor type, mean follow-up time, OCT device type, OCT tive status between the children of the same age, Avery et al.
parameters, and conclusions. [7] recommended the use of a standardized visual acuity as-
Consecutiveness of patients’ inclusion, representativeness sessment in all the future OPG clinical trials: the authors sug-
of the samples, the comparison with the reference standard test gested that Teller acuity test should be used across all age
(i.e., brain and orbit contrast-enhanced MRI), and blinding groups and, when capable, children would complete the
Table 1 Demographic features of the studies included in review

Authors and year Study design No. of patients/no. No. of females (%) Mean age (yrs) No. of No. of Mean age (yrs) Mean follow- Level of
of eyes controls/ females up (mos) evidencea
no. of eyes
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Chang L et al. 2010 [16] Prospective case-series 15/NA 5 (55%); NA (range 6–17; 7–20) 15/NA NA NA (age- and 0 4
3 (50%) race-matched)
Avery RA et al. 2011 [10] Prospective cross-sectional 58/109 40 (68%) 11.6 14/28 65% 11.3 0 3
Fard MA et al. 2013 [21] Prospective cohort 23/38 12 (53%) 5.8 0 – – 24 3
Parrozzani R et al. 2013 [36] Prospective case-controlled 57/114 23 (40%) 7.2 0 – – 0 2
Topcu-Yilmaz P et al. 2014 [41] Prospective case-series 27/NA 15 (55%) 14.5 (NF1 without 17/NA 6 (35%) 12.35 0 4
OPG); 12.6
(NF1 with OPG)
Gu S et al. 2014 [23] Prospective cross-sectional 26/47 NA 5.3; 6.1 0 – – 0 3
Avery RA et al. 2014 [9] Prospective cross-sectional 33/64 18 (54%) 4.8 20/31 7 (35%) 8.7 0 3
Avery RA et al. 2014 [4] Prospective cross-sectional Intra-visit cohort: 61%; 58.6% Intra-visit cohort, 4.6; 0 – – 6 3
and longitudinal inter-visit cohort, 5.7
59/NA; inter-visit
cohort: 29/NA
Avery RA et al. 2014 [5] Prospective cohort Intra-visit cohort: 27 (64%); NA 5.3; NA 0 – – 6 3
42/45; inter-visit
cohort: 21/25
Rajjoub RD et al. 2015 [39] Prospective cohort 42/62 Abnormal vision, 14 Abnormal vision, 0 – – 4.2 3
(64%); normal 10.7; normal
vision, 16 (67%) vision, 8.5
Avery RA et al. 2015 [6] Prospective cohort New vision loss, 5 (50%); 30 (67%) 6.9; 6.5 0 – – 16.5; 13.4 3
7/10; stable
vision, 39/45

NA information not available, NF1 neurofibromatosis-1, OPG optic pathway glioma

Level of evidence according to Oxford Centre for Evidence-Based Medicine 2011 [26]
Childs Nerv Syst

computer-based HOTV testing in addition to the Teller acuity The Response Evaluation in Neurofibromatosis and
test. Both tests have been validated in pediatric clinical trials, Schwannomatosis (REiNS) International Collaboration was
and the results can be converted in logMAR units [7, 32]. established in 2011 to achieve consensus about the methodol-
The need of standardized visual acuity testing is also ogy of clinical trials regarding NF [38]. One of the seven
sustained by the observation we made during the analysis of working groups of the REiNS Collaboration focuses on visual
the 11 studies: the methods of visual acuity assessment were outcomes. According to this committee (2013) [22], visual
highly variable—Teller acuity test [4], HOTV test [9, 10], Lea acuity should be the main functional outcome measure in clin-
fig. [36], Sloan low-contrast acuity chart [10], E-game [21], or ical trials of children with NF1-associated OPG. The recom-
Snellen chart [36]. Some papers did not specify the employed mended tests are Teller acuity charts and HOTV, and the re-
methods for visual acuity testing, although it was stated that sults should be reported in logMAR, considering the age-
age-adapted tests were used [4–6, 23]. However, an observa- specific norms [22]. The other recommended outcomes are
tion we consider worth mentioning is that low-contrast acuity the presence of optic disc pallor and Children’s Visual
measures may be more sensitive to visual pathway damage Function Questionnaire—given the importance of including
from OPG in comparison with high-contrast visual acuity patient-reported outcomes in clinical trials. Assessment of vi-
measures [10]. sual field, color vision, strabismus, nystagmus, optic disc
Visual field examination also requires patient’s collabora- swelling, proptosis, or visual evoked potentials are not recom-
tion, and the results are highly variable [31]. Confrontation mended [22]. OCT was not included among the recommended
test, Goldmann kinetic perimetry, or static automated investigations due to lack of data [22].
perimetry can be used depending on the child’s age.
However, there is high test-retest variability, and the results OCT technology
are hard to quantify [31]. Although the visual field was tested
by the majority of the studies included in review, the results Retinal OCT is an imaging technique analogous to ultrasound
were not interpreted alone, but in association with concurrent as it is based on low-coherence interferometry and measures
visual acuity deficits. the intensity of the back-scattered light from the tissue. Time-
Color vision loss usually accompanies visual acuity decline domain was the first generation of OCT technology, and the
in NF1-associated OPG, and the presence of visual acuity loss first in vivo OCT studies of the human retina were performed
without color vision loss is indicative of refractive error, am- in 1993 [20]. Time-domain OCT offers an axial resolution of
blyopia, a functional disorder, or lack of cooperation [31]. 10 μm and acquires 400 A-scans/s. The second generation of
None of the 11 studies investigated the possible correlation OCT is called spectral-domain (or Fourier-domain) OCT and
between color vision and visual acuity, visual field, or OCT became commercially available in 2006. Spectral-domain
parameters in children with OPG. OCT permits an axial resolution of 1–5 μm and the acquisition
In a study investigating the post-treatment functional of up to 52,000 A-scans/s, with tridimensional reconstruction
changes in 21 children with OPG, Magli et al. [33] assessed of the examined tissue [1, 20].
the changes of contrast sensitivity. According to the presented Retinal OCT was primarily used in ophthalmological con-
data, in patients with normal visual acuity at diagnosis, con- ditions, and after a period of clinical employment, studies
trast sensitivity seemed to be a better indicator of tumor pro- investigating neurological diseases (e.g., multiple sclerosis,
gression than visual acuity [33]. Contrast sensitivity was not Parkinson’s disease) were conducted. Moreover, the majority
evaluated in the articles included in the present review. of OCT devices are table-mounted and are being used in adult
Visual evoked potentials (VEP) have been suggested as patients. Therefore, it is not surprising that we found only 11
a screening or follow-up method in children with NF1, eligible papers using retinal OCT in children with OPG. The
but there was not enough evidence to recommend it first reported study we identified was published in 2010 [16].
[31]. A review on the role of VEP in the assessment of Different types of OCT devices were utilized in the studies
OPG [42] demonstrated that the use of VEP as a routine included in our review. The majority were table-mounted,
screening test in OPG is not indicated. The studies includ- either time-domain or Spectral-domain OCT. A handheld
ed in the cited review presented limitations regarding the spectral-domain OCT equipment (Bioptigen, Durham, NC)
sample sizes, differences in VEP protocol, variability in was also successfully used in young children [4–6, 9, 23,
interpretation of the VEP results, and the absence of ap- 39]. For all OCT devices, the duration of retinal scan was of
propriate control groups in some studies [42]. Iannaccone a few seconds for each eye and the main examination proto-
et al. [27] demonstrated that VEP abnormalities were also cols included the assessment of the retinal nerve fiber layer
present in children with NF1 even in the absence of OPG (RNFL) thickness around the optic nerve papilla and the ret-
or other brain tumors. These findings prove that VEP inal thickness in the macular area [4–6, 9, 10, 16, 23, 36, 39,
interpretation in children with NF1 can be particularly 41]. Retinal ganglion cell loss was expressed as RNFL thin-
challenging. ning and/or decreased macular thickness.
Childs Nerv Syst

Particularities of OCT use in children the RNFL thickness was influenced mostly by ocular ax-
ial length and refractive error while it was independent of
One aspect to be considered in the interpretation of OCT re- age [40].
sults in children is the normative reference for the young pop- – Barrio-Barrio et al. (2013) conducted a multicenter study
ulation. Unlike in the case of adult patients, for the commer- in which 283 Spanish children aged between 4 and 17
cially available OCT devices, the results are not automatically were enrolled; the examination was performed with
compared with normal age-matched population and the inter- Cirrus spectral-domain OCT, and a positive correlation
pretation must be done either by follow-up (comparing the was found between RNFL thickness and ocular refraction
results with the baseline), by creating a normative database only [11].
or by using one which it has already been published. – Yanni et al. (2013) examined 83 North American children
The studies included in the present review used the follow- aged between 5 and 15 using Spectralis spectral-domain
up method and/or included small-sized samples of controls, OCT (Heidelberg Engineering GmbH, Heidelberg,
equivalent to a mini normative database (Tables 1, 2). Fard Germany), and the only parameter significantly correlated
et al. [21] used the follow-up method and suggested that age- with age was central subfield macular thickness [44]. Other
related RNFL thickness decline should be considered when studies also reported a statistically significant correlation
discriminating between the physiologic and the pathologic between OCT macular parameters and age [2, 11, 24].
process. To the best of our knowledge, there is only one
OCT study investigating the age-related RNFL decline in The reproducibility of OCT parameters was investigated by
which both children and adults were enrolled [35]; the results three of the 11 studies included in our review [4, 5, 39].
suggest that the RNFL loss is maximum after the age of 50 Rajjoub et al. [39] reported the use of BEye-Tracking^ OCT
[35]. The other studies were conducted on adults only, and the feature (Spectralis OCT) in children with OPG. The authors
results were extrapolated to pediatric population: the presence observed that adding BEye-Tracking^ feature to the scanning
of a linear decrease of average RNFL thickness with age was protocol offered excellent reproducibility of RNFL measures
documented [25, 30], with a decline range between − 0.16 and [39], although the studies using the handheld OCT device also
− 0.44 μm/year [30]. Age-related RNFL loss was not uniform reported a good reproducibility of the measures [4, 5].
in all the quadrants [30, 35]. Another element to be considered in young children is
Nevertheless, several normative OCT reference values for performing the OCT scan during general anesthesia. The au-
the pediatric population are now available and no correlation thors who reported the use of handheld OCT device per-
between RNFL thickness and age was found, as seen in the formed the examination during the sedation indicated for
following recently published results: MRI evaluation [4–6, 9, 23]. The ability to acquire high-
resolution spectral-domain OCT in young children with
– Gürağaç et al. (2016) examined 318 Turkish children OPG who cannot cooperate with vision testing or table-
aged between 3 and 17 using Cirrus Spectral-domain mounted OCT imaging is highly relevant because most pa-
OCT (Carl Zeiss Meditec, Dublin, CA) and the strongest tients become symptomatic and require treatment during early
predictors of RNFL thickness were ocular axial length, childhood [9]. However, Avery et al. [4] brought into question
refraction, and optic nerve rim area [24]. whether exposure to additional anesthesia for obtaining a thor-
– Pawar et al. (2014) examined 120 Indian children aged ough OCT evaluation would be ethically acceptable or not.
between 5 and 17 using stratus time-domain OCT (Carl Although the handheld OCT device offers the advantage of
Zeiss Meditec, Dublin, CA), and age had no statistical portability, there are also some limitations: the variability of
significant effect on RNFL thickness, unlike ocular re- ocular axial lengths in children may influence the OCT sam-
fraction which it had a significant effect on RNFL thick- pling [9], and the assessment of the image/signal quality and
ness [37]. retinal segmentation cannot be performed until the end of the
– Al-Haddad et al. (2014) examined 108 Middle East chil- imaging session [5].
dren aged between 6 and 17 using Cirrus spectral-domain Chemotherapy was also incriminated as a possible cause of
OCT, and RNFL measurements did not correlate with RNFL loss in children with OPG [5, 8], but further research is
age, but it did show a positive correlation with refraction needed to address this issue.
– Zhu et al. (2013) evaluated 1955 Chinese children aged The role of OCT in OPG assessment
12 using iVue-100 spectral-domain OCT (Optovue,
Fremont, CA), and the RNFL thickness had no significant Table 2 reveals clinical features of the studies. Taking into
correlation with age [46]. consideration the fact that the OCT devices and scanning pro-
– Rao et al. (2013) examined 74 Indian children aged be- tocols were variable between the studies, and there were also
tween 4 and 17 using Cirrus spectral-domain OCT, and differences regarding sampling (Tables 1, 2) and methods of
Table 2 Clinical features of the studies included in review

Authors and year Tumor type Type of OCT OCT protocol OCT parameters Comparison Conclusion of study

Chang L et al. 2010 [16] 9 pts.: NF1 with OPG TD-OCT (Stratus/Carl Fast macular Macular thickness, RNFL patients vs controls OCT can be used to detect RNFL
6 pts.: NF1 without OPG Zeiss Meditec) thickness, fast thinning secondary to OPG in NF1
RNFL thickness subjects. This objective tool shows
promise as a useful adjunct to
routine clinical ophthalmologic
evaluation in children with NF1.
Avery RA et al. 2011 [10] 48 pts.: sporadic + TD-OCT (Stratus/Carl Fast RNFL thickness RNFL High-contrast Eyes of most children with OPG and
NF1-associated OPG Zeiss Meditec) visual acuity, decreased RNFL thickness had
10 pts.: NF1 without OPG low-contrast let- abnormal visual acuity or visual
ter acuity field loss.
Fard MA et al. 2013 [21] 9 pts.: sporadic OPG SD–OCT Posterior pole Grid retinal thickness, Baseline vs RNFL and posterior pole retinal
14 pts.: NF1 with OPG (Spectralis/Heidelb- thickness map, RNFL 24-months data thickness may be helpful in
erg Engineering) RNFL map monitoring OPG.
Parrozzani R et al. 2013 [36] 15 pts.: NF1 with OPG SD–OCT RNFL thickness RNFL Visual acuity, RNFL is superior to visual function
42 pts.: NF1 without OPG (Spectralis/Heidelb- ophthalmoscopic assessment and optic disc
erg Engineering) optic disc evaluation as a clinical screening
evaluation tool for OPG.
Topcu-Yilmaz P et al. 2014 [41] 17 pts.: NF1 with OPG TD–OCT RNFL thickness, RNFL, macular thickness Patients vs controls RNFL thinning can be a helpful
10 pts.: NF1 without OPG (Stratus/Carl Zeiss retinal macular marker for the detection of OPG in
Meditec) thickness NF1 patients.
Gu S et al. 2014 [23] 26 pts.: sporadic + Handheld SD-OCT Macular scan, RNFL Ganglion cell—inner Normal vs Ganglion cell layer—inner plexiform
NF1-associated OPG (HH OCT/Bioptigen) thickness plexiform layer abnormal vision layer thickness could be used as a
thickness, RNFL surrogate marker of vision in
children with OPG.
Avery RA et al. 2014 [9] 25 pts.: NF1 with OPG Handheld SD-OCT 6 mm × 6 mm optic RNFL (obtained using a Visual acuity, Measures of RNFL thickness acquired
8 pts.: sporadic OPG (HH OCT/Bioptigen) nerve head scan, en custom-made soft- visual field with handheld OCT during
face volume ware) sedation can differentiate between
young children with and without
vision loss from OPG. For young
children who do not cooperate with
vision testing, handheld OCT
measures may be a surrogate
marker of vision.
Avery RA et al. 2014 [4] 35 pts.: NF1 with OPG Handheld SD-OCT 6 × 6 × 2 mm RNFL (obtained using a Intra- vs inter-visit RNFL measures acquired with
10 pts.: NF1 without OPG (HH OCT/Bioptigen) volumes acquired custom-made soft- cohort handheld OCT during sedation
14 pts.: sporadic OPG over the optic nerve ware) demonstrate good intra- and
head inter-visit reproducibility.
Handheld OCT has the potential to
monitor progressive optic neuropa-
thies in young children who have
difficulty cooperating with tradi-
tional OCT devices.
Childs Nerv Syst
Table 2 (continued)

Authors and year Tumor type Type of OCT OCT protocol OCT parameters Comparison Conclusion of study
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Avery RA et al. 2014 [5] 25 pts.: NF1 with OPG Handheld SD-OCT Macular volume Total macular thickness, Intra- vs inter-visit Macular volumes acquired with
5 pts.: NF1 without OPG (HH OCT/Bioptigen) ganglion cell—inner cohort handheld OCT demonstrated
12 pts.: sporadic OPG plexiform layer excellent reproducibility of total
thickness retinal thickness and ganglion
cell—inner plexiform layer
thickness measures.
Rajjoub RD et al. 2015 [39] 28 pts.: sporadic + SD-OCT RNFL thickness + eye RNFL Normal vs SD-OCT with eye tracking
NF-associated OPG (Spectralis/Heidelberg tracking feature abnormal vision demonstrates highly reproducible
2 pts.: craniopharyngioma Engineering) RNFL thickness measures in
1 pt.: prolactinoma children with non-glaucomatous
1 pt.: Langerhans cell optic neuropathy.
1 pt.: demyelination
Avery RA et al. 2015 [6] 46 pts.: sporadic + Handheld SD-OCT Optic nerve head cube; RNFL Visual acuity, Children experiencing vision loss
NF1-associated OPG (HH RNFL measure visual field from their OPG frequently
OCT/Bioptigen) or using Nsite demonstrate a ≥ 10% decline of
table-mounted analytics and RNFL thickness in 1 or more
SD-OCT TruTrack anatomic sectors. Global average
(Spectralis/Heidelb- and the inferior quadrant
erg Engineering) demonstrated the best positive and
negative predictive values. RNFL is
a surrogate marker of vision and
could be helpful in making
treatment decisions for children
with OPG.

NF1 neurofibromatosis-1, OPG optic pathway glioma, RNFL circumpapillary retinal nerve fiber layer, SD-OCT spectral-domain optical coherence tomography, TD-OCT time-domain optical coherence
Childs Nerv Syst

testing visual acuity, a reliable statistical comparison between reported that the papillomacular bundle measures were highly
the studies was not possible. variable between examinations, probably due to it being the
The studies tested the hypothesis that retinal OCT could be thinnest area and the most susceptible to segmentation or mo-
a surrogate marker of vision in children with OPG and, con- tion artifacts. The authors advise clinicians to be cautious
sequently, a screening [6, 9, 10, 23, 36, 41] or follow-up tool when interpreting small changes in the thickness of the
[4–6, 16, 21, 39]. papillomacular bundle [39].
The results of the studies investigating OCT as a screening Although OCT imaging may be limited by subject cooper-
tool for the detection of OPG [6, 8, 9, 23, 36, 41] indicated ation, it is less limited than the evaluation of visual function,
thinner OCT measures in patients with OPG compared to requiring only seconds of cooperation instead of minutes as in
controls and also a correlation between visual acuity status the latter [16, 36].
and RNFL or macular thickness. All the studies included in The major limitations of the studies are the small number of
review showed that OCT may be a useful instrument to detect patients and the short follow-up time (Table 1). Other limita-
the presence of OPG in children with or without NF1 and to tions are as follows: incomplete MRI data (either baseline or
identify visual decline (Table 2). Patients with OPG who had concurrent MRI) [16], undilated refraction to determine best
thinner RNFL even in the presence of normal visual function corrected visual acuity [10], lack of OCT data for healthy
were also identified [10, 16, 41]. Avery et al. [9] reported an control children [21], or variable frequency of study visits [6].
average RNFL thickness of approximately 80 μm as threshold
value for visual loss: RNFL thickness of > 80 μm was asso-
ciated with normal visual acuity, whereas lower RNFL thick- OCT use in other types of visual pathway tumors
ness was associated with worse visual acuity. For the children in pediatric population
who did not cooperate to perform the examination at a table-
mounted OCT device, the retinal scan with a handheld OCT Bialer et al. [12] investigated the use of OCT for monitoring
during sedation was also considered a marker of vision [9]. optic neuropathy in children with craniopharyngioma. The
Parrozzani et al. [36] demonstrated that RNFL is superior to authors conducted a retrospective study in which RNFL thick-
visual function assessment and optic disc evaluation as a clin- ness was assessed in 20 children treated in the same pediatric
ical screening tool for OPG in children with NF1. medical center. The results demonstrated that thinner RNFL
Other studies investigated the role of retinal OCT scan for on OCT was associated with poorer visual acuity and visual
follow-up evaluation. The results indicate that RNFL may be a field loss [12]. These findings were congruent with the results
surrogate marker of vision [4–6, 16, 39] and could be helpful of the studies investigating the use of OCT in OPG.
in making treatment decisions for children with OPG [6]. A
RNFL thickness decline of 10 to 15% in comparison with the
baseline thickness was considered clinically significant and Conclusion
regarded as disease progression [4]; whereas for the macular
parameters, a change of > 10% in the ganglion cell-inner plex- Retinal OCT is a promising tool to be considered as a screen-
iform layer thickness was also considered clinically signifi- ing or monitoring test for OPG in children, and further re-
cant [5]. Avery et al. [6] noticed that a greater amount of search is encouraged. Multicenter clinical research using stan-
RNFL loss may need to occur in patients with normal RNFL dardized protocols of both visual function assessment and
thickness compared to patients with already reduced RNFL retinal OCT scanning is needed.
thickness, who may require less of a decline to experience MRI of the brain and orbits remains the gold standard for
visual loss. OPG diagnosis, and the presence of clinical or neuroimaging
We mention the exceptional situation of two patients with progression represents an indication for therapy.
sporadic glioma isolated to the optic nerve who demonstrated
increases of RNFL thickness of less than 20 μm in the absence
of optic disc edema [6]. The authors considered that axonal
stasis may be responsible of this small increase in RNFL
Compliance with ethical standards
thickness, especially in these two patients with preexisting
optic nerve pallor [6]. Conflicts of interest/disclosures The authors declare that they have no
The majority of studies included RNFL thickness evalua- financial or other conflicts of interest in relation to this research and its
tion, but there was a variety of the macular scanning protocols publication.
(Table 2). Studies conducted on adult patients with optic path-
way tumors showed that the results provided by different OCT
Ethical approval For this type of study, formal consent is not required.
devices or using different macular scanning protocols were This article does not contain any studies with human participants or an-
not comparable [17, 34]. Moreover, Rajjoub et al. [39] imals performed by any of the authors.
Childs Nerv Syst

References 19. Dodgshun AJ, Elder JE, Hansford JR, Sullivan MJ (2015) Long-
term visual outcome after chemotherapy for optic pathway glioma
in children: site and age are strongly predictive. Cancer 121:4190–
1. Adhi M, Duker JS (2013) Optical coherence tomography—current 4196
and future applications. Curr Opin Ophthalmol 24(3):213–221 20. Drexler W, Fujimoto JG (2008) State-of-the-art retinal optical co-
2. Al-Haddad C, Barikian A, Jaroudi M, Massoud V, Tamim H, herence tomography. Prog Retin Eye Res 27(1):45–88
Noureddin B (2014) Spectral domain optical coherence tomogra- 21. Fard MA, Fakhree S, Eshraghi B (2013) Correlation of optical
phy in children: normative data and biometric correlations. BMC coherence tomography parameters with clinical and radiological
Ophthalmol. progression in patients with symptomatic optic pathway gliomas.
3. Avery RA, Bouffet E, Packer RJ, Reginald A (2013) Feasibility and Graefes Arch Clin Exp Ophthalmol 251:2429–2436
comparison of visual acuity testing methods in children with neu- 22. Fisher MJ, Avery RA, Allen JC, Ardern-Holmes SL, Bilaniuk LT,
rofibromatosis type 1 and/or optic pathway gliomas. Invest Ferner RE et al (2013) Functional outcome measures for NF1-
Ophthalmol Vis Sci 54:1034–1038 associated optic pathway glioma clinical trials. Neurology
4. Avery RA, Cnaan A, Schuman JS, Chen CL, Glaug NC, Packer RJ 81(Suppl 1):S15–S24
et al (2014) Reproducibility of circumpapillary retinal nerve fiber
23. Gu S, Glaug N, Cnaan A, Packer RJ, Avery RA (2014) Ganglion
layer measurements using handheld optical coherence tomography
cell layer-inner plexiform layer thickness and vision loss in young
in sedated children. Am J Ophthalmol 158(4):780–787
children with optic pathway gliomas. Invest Ophthalmol Vis Sci 55:
5. Avery RA, Cnaan A, Schuman JS, Chen CL, Glaug NC, Packer RJ 1402–1408
et al (2014) Intra- and inter-visit reproducibility of ganglion cell—
24. Gürağaç FB, Totan Y, Güler E, Tenlik A, Ertuğrul IG (2016)
inner plexiform layer measurements using handheld optical coher-
Normative spectral domain optical coherence tomography data in
ence tomography in children with optic pathway gliomas. Am J
healthy Turkish children. Semin Ophthalmol.
Ophthalmol 158(5):916–923
6. Avery RA, Cnaan A, Schuman JS, Trimboli-Heidler C, Chen CL,
25. Harwerth RS, Wheat JL (2008) Modeling the effects of aging on
Packer RJ et al (2015) Longitudinal change of circumpapillary ret-
retinal ganglion cell density and nerve fiber layer thickness. Graefes
inal nerve fiber layer thickness in children with optic pathway gli-
Arch Clin Exp Ophthalmol 246:305–314
omas. Am J Ophthalmol 160(5):944–952
26. Howick J, Chalmers I, Glasziou P, Greenhalgh T, Heneghan C,
7. Avery RA, Ferner RE, Listernick R, Fisher MJ, Gutmann DH, Liu
Liberati A, et al. The Oxford 2011 levels of evidence. Oxford
GT (2012) Visual acuity in children with low grade gliomas of the
Centre for Evidence-Based Medicine.
visual pathway: implications for patient care and clinical research. J
aspx?o=5653. Accessed July 2016
Neuro-Oncol 110:1–7
8. Avery RA, Fisher MJ, Liu GT (2011) Optic pathway gliomas. J 27. Iannaccone A, McCluney RA, Brewer VR, Spiegel PH, Taylor JS,
Neuroophthalmol 31:269–278 Kerr NC et al (2002) Visual evoked potentials in children with
9. Avery RA, Hwang EI, Ishikawa H, Acosta MT, Hutcheson KA, neurofibromatosis type 1. Doc Ophthalmol 105:63–81
Santos D et al (2014) Handheld optical coherence tomography dur- 28. Jindahra P, Petrie A, Plant GT (2009) Retrograde trans-synaptic
ing sedation in young children with optic pathway gliomas. JAMA retinal ganglion cell loss identified by optical coherence tomogra-
Ophthalmol 132(3):265–271 phy. Brain 132:628–634
10. Avery RA, Liu GT, Fisher MJ, Quinn GE, Belasco JB, Phillips PC 29. Keller J, Sanchez-Dalmau BF, Villoslada P (2014) Lesions in the
et al (2011) Retinal nerve fiber layer thickness in children with optic posterior visual pathway promote trans-synaptic degeneration of
pathway gliomas. Am J Ophthalmol 151(3):542–549 retinal ganglion cells. PLoS One 9(5):e97444.
11. Barrio-Barrio J, Noval S, Galdos M, Ruiz-Canela M, Bonet E, 1371/journal.pone.0097444
Capote M et al (2013) Multicenter Spanish study of spectral- 30. Leung CKS, Yu M, Weinreb RN, Ye C, Liu S, Lai G et al (2012)
domain optical coherence tomography in normal children. Acta Retinal nerve fiber layer imaging with spectral-domain optical co-
Ophthalmol 91(1):e56–e63 herence tomography. Ophthalmology 119:731–737
12. Bialer OY, Goldenberg-Cohen N, Toledano H, Snir M, Michowiz S 31. Listernick R, Ferner RE, Liu GT, Gutmann DH (2007) Optic path-
(2013) Retinal NFL thinning on OCT correlates with visual loss in way gliomas in neurofibromatosis-1: controversies and recommen-
pediatric craniopharyngioma. Can J Ophthalmol 48:494–499 dations. Ann Neurol 61:189–198
13. Binning MJ, Liu JK, Kestle JRW, Brockmeyer DL, Walker ML 32. Listernick R, Louis DN, Packer RJ, Gutmann DH (1997) Optic
(2007) Optic pathway gliomas: a review. Neurosurg Focus 23(5):E2 pathway gliomas in children with neurofibromatosis-1: consensus
14. Caen S, Cassiman C, Legius E, Casteels I (2015) Comparative statement from the NF1 optic pathway glioma task force. Ann
study of the ophthalmological examinations in neurofibromatosis Neurol 41(2):143–149
type 1. Proposal for a new screening algorithm. Eur J Paedriatr 33. Magli A, Forte R, Cinalli G, Esposito F, Parisi S, Capasso M et al
Neurol 19:415–422 (2013) Functional changes after treatment of optic pathway paedi-
15. Cassiman C, Legius E, Spileers W, Casteels I (2013) atric low-grade gliomas. Eye 27:1288–1292
Ophthalmological assessment of children with neurofibromatosis 34. Monteiro MLR, Cunha LP, Vessani RM (2008) Comparison of
type 1. Eur J Pediatr 172:1327–1333 retinal nerve fiber layer measurements using stratus OCT fast and
16. Chang L, El-Dairi MA, Frempong TA, Burner EL, Bhatti MT, regular scan protocols in eyes with band atrophy of the optic nerve
Young TL et al (2010) Optical coherence tomography in the eval- and normal controls. Arq Bras Oftalmol 71(4):534–539
uation of neurofibromatosis type-1 subjects with optic pathway 35. Parikh RS, Parikh SR, Sekhar GC, Prabakaran S, Babu JG, Thomas
gliomas. J AAPOS 14:511–517 R (2007) Normal age-related decay of retinal nerve fiber layer
17. Costa-Cunha LVF, Cunha LP, Malta RFS, Monteiro MLR (2009) thickness. Ophthalmology 114:921–926
Comparison of fourier-domain and time-domain optical coherence 36. Parrozzani R, Clementi M, Kotsafti O, Miglionico G, Trevisson E,
tomography in the detection of band atrophy of the optic nerve. Am Orlando G et al (2013) Optical coherence tomography in the diag-
J Ophthalmol 147:56–63 nosis of optic pathway gliomas. Invest Ophthalmol Vis Sci 54:
18. Danesh-Meyer HV, Wong A, Papchenko T, Matheos K, Stylli S, 8112–8118
Nichols A et al (2015) Optical coherence tomography predicts vi- 37. Pawar N, Maheshwari D, Ravindran M, Ramakrishnan R (2014)
sual outcome for pituitary tumors. J Clin Neurosci 22:1098–1104 Retinal nerve fiber layer thickness in normal Indian pediatric
Childs Nerv Syst

population measured with optical coherence tomography. Indian J 43. Wan MJ, Ulrich NJ, Manley PE, Kieran MW, Goumnerova LC,
Ophthalmol 62(4):412–418 Heidary G (2016) Long-term visual outcomes of optic pathway
38. Plotkin SR, Blakeley JO, Dombi E, Fisher MJ, Hanemann CO, gliomas in pediatric patients without neurofibromatosis type 1. J
Walsh KS et al (2013) Achieving consensus for clinical trials. The Neurooncol doi.
REiNS international collaboration. Neurology 81(Suppl 1):S1–S5 44. Yanni SE, Wang J, Cheng CS, Locke KI, Wen Y, Birch DG et al
39. Rajjoub RD, Trimboli-Heidler C, Packer RJ, Avery RA (2015) (2013) Normative reference ranges for the retinal nerve fiber layer,
Reproducibility of retinal nerve fiber layer thickness measures macula, and retinal layer thickness in children. Am J Ophthalmol
using eye-tracking with spectral-domain optical coherence tomog- 155(2):354–360
raphy in children with non-glaucomatous optic neuropathy. Am J 45. Yoneoka Y, Hatase T, Watanabe N, Jinguji S, Okada M, Takagi M
Ophthalmol 159(1):71–77 et al (2015) Early morphological recovery of the optic chiasm is
40. Rao A, Sahoo B, Kumar M, Varshney G, Kumar R (2013) Retinal associated with excellent visual outcome in patients with compres-
nerve fiber layer thickness in children <18 years by spectral-domain sive chiasmal syndrome caused by pituitary tumors. Neurol Res
optical coherence tomography. Semin Ophthalmol 28(2):97–102 37(1):1–8
41. Topcu-Yilmaz P, Kasim B, Kiratli H (2014) Investigation of retinal 46. Zhu BD, Li SM, Li H, Liu LR, Wang Y, Yang Z, Anyang
nerve fiber layer thickness in patients with neurofibromatosis-1. Jpn Childhood Eye Study Group et al (2013) Retinal nerve fiber layer
J Ophthalmol 58:172–176 thickness in a population of 12-year-old children in central China
42. Van Mierlo C, Spileers W, Legius E, Casteels I, Cassiman C (2013) measured by iVue-100 spectral-domain optical coherence tomog-
Role of visual evoked potentials in the assessment and management raphy: the Anyang childhood eye study. Invest Ophthalmol Vis Sci
of optic pathway gliomas in children. Doc Ophthalmol 127:177–190 54(13):8104–8111