Download Optical Coherence Tomography in Pediatric Ophthalmology: Current

■
R E V I E W
Optical Coherence
Tomography in Pediatric
Ophthalmology: Current
Roles and Future
Directions
Tarek Alasil, MD; Pearse A. Keane, MD; Dawn A.
Sim, MD; Adnan Tufail, MD; Michael E. Rauser, MD
ABSTRACT: The application of existing optical coherence tomography (OCT) technology to the pediatric
population is limited in both the design specification
of the device and its hardware. However, the potential of OCT in the pediatric population has not been
fully realized. The authors review the literature, highlighting the currently available spectral-domain OCT
technology and summarizing the reported normal pediatric OCT parameters for retinal nerve fiber layer
and macular thickness. They also review the pediatric ophthalmological conditions in which OCT has
been used and discuss advancements in OCT design
and their potential applications to the pediatric population. The use of OCT in pediatric populations is
likely to increase greatly in the coming years, aiding
clinical decision-making and providing new insights
into pediatric disease pathophysiology.
[Ophthalmic Surg Lasers Imaging Retina. 2013;44:S19-S29.]
From the Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts (TA); NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute
of Ophthalmology, London, United Kingdom (PAK, DAS, AT); and Department
of Ophthalmology, Loma Linda University, Loma Linda, California (MER).
Originally submitted February 11, 2013. Accepted for publication May 7, 2013.
Drs. Keane and Tufail received a proportion of their funding from the Department of Health’s NIHR Biomedical Research Centre for Ophthalmology at
Moorfields Eye Hospital and UCL Institute of Ophthalmology. Dr. Sim receives
funding from Fight For Sight (UK), Grant 1987.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Tarek Alasil, MD, Department of Ophthalmology,
Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114.
doi: 10.3928/23258160-20131101-04
November/December 2013 · Vol. 44, No. 6 (Suppl)
■
INTRODUCTION
In the past decade, optical coherence tomography
(OCT) has not only gained popularity in the practice
of clinical ophthalmology, but its parameters serve as
endpoint measures in many large multicenter clinical
trials.1,2 The popularity of OCT is largely because of its
properties as a noninvasive investigative technique, its
speed of image acquisition, and its ability to provide
clinically relevant and reproducible measures useful
in the diagnosis and monitoring of disease. In adult
populations, OCT was initially adopted for assessment of diseases with subtle clinical findings, such as
abnormalities of the vitreoretinal interface.3 With the
introduction of new pharmacotherapies for age-related macular degeneration (AMD), and more recently
for retinal vascular diseases such as diabetic macular
edema (DME), its use has become ubiquitous among
retina specialists. In contrast, the use of OCT in pediatric populations has lagged behind that in adult populations. This may be explained in large part by the differing nature of diseases affecting pediatric populations,
with the absence of a major disease such as neovascular AMD driving adoption. Limitations of OCT devices
may also be a contributing factor, however, leading to
difficulties in acquisition of OCT images in noncompliant younger children and infants. Furthermore,
OCT image acquisition protocols are currently focused
on scanning of the macula, a potential disadvantage
given that many pediatric ophthalmic diseases involve
extramacular pathologies.
The application of existing OCT technology to
the pediatric population is limited both in the design
specification of the machine and in its hardware. The
size of the machines, the height and position of their
headrests, the time taken to acquire images, and sensitivity to small changes in positioning often preclude
use in a moving child. As a result, OCT is sometimes
performed in anesthetized children (an invasive requirement that significantly impacts the frequency of
usage). In anesthesia, the requirement for supine positioning may also lead to changes in the anatomical
positioning of normal ocular structures (eg, the lens
and ciliary body) and fluctuations in pathologic features (eg, fluidic shifts in the cases of edema or subretinal fluid). This may affect OCT’s ability to accurately
assess disease activity and make direct comparisons
with adult populations difficult.
Rapid advances in OCT technology, with enhanced
image acquisition speeds and wide-field technology,
S19
may allow OCT to be used as a routine investigative
tool in the pediatric population in the near future. In
this review, we summarize the pediatric ophthalmological conditions in which OCT has been used and
discuss advancements in OCT design, and their potential applications in pediatric patients.
surgery. The use of microscope-mounted SD-OCT
has enabled wide-field noncontact real-time crosssectional imaging of retinal structure and augmented
intrasurgical microscopy for intraocular visualization.9,10 This technology may be of particular interest
for use in children.
CURRENT TECHNOLOGY
Anterior-Segment OCT
Spectral-Domain OCT
Stratus OCT (Carl Zeiss Meditec, Dublin, CA), the
first OCT system to be widely adopted by ophthalmologists, provides images with relatively high axial
resolution (~10 μm in tissue). However, the major
limitation of Stratus OCT is its need for a moving
reference mirror and thus a relatively slow image
acquisition speed (400 A-scans per second). In Stratus OCT, A-scans are acquired as a function of time,
and thus such devices are often referred to as timedomain OCT (TD-OCT). More recently, commercial
OCT systems have employed techniques to measure
OCT A-scans as a function of frequency, and this
generation of OCT technology is referred to as spectral-domain or Fourier-domain OCT. The major advantage of this approach is a greatly enhanced image
acquisition speed, 50 to 100 times faster than Stratus
OCT.4 Greater speed also allows more of the retina to
be sampled in a single image set and may also facilitate OCT image acquisition in pediatric populations.
Commercially available spectral-domain OCT (SDOCT) devices (eg, Spectralis, Heidelberg Engineering, Germany) have also incorporated eye-tracking
technology. Using this technology, multiple images
can be obtained from the same location and averaged to enhance visualization of fine structures.5,6
Real-time eye tracking also compensates for many of
the involuntary eye movements that can occur during image acquisition and result in motion artifacts,
which may prove useful in poorly compliant pediatric populations.
Anterior-segment OCT (AS-OCT) is a noninvasive technology capable of capturing high-resolution
images of the anterior segment, particularly of the
cornea and anterior chamber angles. Because ASOCT requires less patient cooperation relative to ultrasound biomicroscopy, it may prove particularly
useful in pediatric populations.11 Despite this, its
potential in this regard remains largely untapped.
HEALTHY PEDIATRIC POPULATIONS
SD-OCT has been successfully converted into a
handheld device by disassembling the camera unit
from the base (by removing the M6 Allen screw
from the rotational bearing at the bottom of the arc
guide). Subsequently, the camera head turns free
and is supported by holding the camera handle at
the back of the mount and gently lifting it off the
base of the instrument. This modification enabled
the imaging of supine and unanesthetized infants
in the office.7,8
Intraoperative SD-OCT has provided new insight
into the changes to retinal anatomy during macular
To make full use of the OCT information, a comparison with age-matched population-derived normative data is needed to identify deviations from
the normal range. Unfortunately, only limited information is available for healthy human populations
younger than 18 years of age. Normative pediatric
OCT data should facilitate the use of OCT in assessing childhood glaucoma and a variety of other pediatric ocular diseases.
Using Stratus OCT, Samarawickrama et al., recently reported the results of the Sydney Childhood
Eye Study, a population-based study examining
childhood eye conditions in Australia.12 During the
2003-2005 period, students in grades 1 (median age:
six years) and 7 (median age: 12 years) were examined. This study concluded that normal children,
6 and 12 years of age and of East Asian ethnicity,
had a significantly thicker retinal nerve fiber layer
(RNFL) — 3% and 12%, respectively — when compared to those of European Caucasian ethnicity (P <
.001). El-Dairi et al collected a normative database of
RNFL thicknesses in the eyes of 286 healthy children
aged 3 to 17 years using Stratus OCT.13 Black children had a larger RNFL thickness, when compared
with white children.
Leung et al studied the normative RNFL thickness values of 104 children in Hong Kong, aged
between 6 and 18 years, using Stratus OCT.14 In
these children, the thickness of the RNFL showed
a significant negative correlation with the axial
length of the eye. Salchow et al measured the peripapillary RNFL thickness in 92 eyes of 92 healthy
children (ages 4 to 17 years) by using OCT.15 They
observed a large variation in RNFL thicknesses in
healthy children, with a significant refractive effect
on measurements.
S20
Ophthalmic Surgery, Lasers & Imaging Retina | Healio.com/OSLIRetina
Handheld and Intraoperative OCT
TABLE
Stratus OCT RNFL normative values in pediatric populations
Year
Author
N
Ethnicity
Age range
(years)
Average
RNFL ± SD (μm)
2005
Ahn et al16
144
Korean
9 - 18
105.5±10.3
2006
Salchow et al15
92
92% Hispanic
4 - 17
107.0±11.1
2009
El-Dairi13
154
Black
109
White
2010
Leung MM14
194
Chinese
2010
Samarawickrama12
909
White
213
East Asian
2011
Qian23
398
Chinese
3 - 17
6 - 17
6 - 12
5 - 18
110.7±8.8
105.9±10.2
113.3±10.3
102.7±1.7
107.7±1.3
112.4±9.2
N = number of healthy eyes; RNFL = retinal nerve fiber layer thickness; SD = standard deviation.
Ahn et al16 studied the RNFL thickness in 144 eyes
of 72 healthy Korean children and adolescents (ages 9
to 18 years) using Stratus OCT. The mean RNFL thickness was 105.5 ± 10.3 μm. The Table summarizes the
stratus OCT RNFL normative values in pediatric populations, which are similar to the range (99 to 103 μm)
reported in the adult TD-OCT literature.17-22
Recent studies have used SD-OCT to evaluate
RNFL thickness in healthy children. Turk et al24 reported an average RNFL thickness of 106.5 ± 9.4 μm
in 107 healthy Turkish children. Tsai et al25 reported
an average RNFL thickness of 109 ±10 μm in 470
healthy Chinese children. Those values are slightly
higher than the adult range (97 to 102 μm) reported
by SD-OCT studies.26-28
Using TD-OCT, Samarawickrama et al12 reported
central macular thickness of 192.5 μm for the 6-yearold healthy group and 197.5 μm for the 12-year-old
healthy group. El-Dairi et al reported the central
macular thickness as 189 μm by using TD-OCT in
healthy children. In their study, black children had
a smaller macular volume and reduced foveal thickness when compared with white children.13 Turk et
al reported central macular thickness of 211.4 μm in
healthy children by using SD-OCT.24
AMBLYOPIA AND STRABISMUS
Amblyopia is characterized by unilateral or bilateral decreased visual acuity, which is caused by
abnormal binocular interaction or visual deprivation during the development of vision.29 There has
been inconsistency about the involvement of the
retina and optic nerve in amblyopia. Recent studies
have used OCT in pediatric populations to investi-
November/December 2013 · Vol. 44, No. 6 (Suppl)
gate whether decreased visual acuity in amblyopia
can be correlated with anatomical abnormalities in
macula and RNFL.
Al-Haddad et al studied the macular thickness in
amblyopia using SD-OCT.30 Central macular thickness was significantly increased in children with
anisometropic amblyopia. Anisometropia alone
did not produce this difference, pointing to a possible correlation between amblyopia and the development of the retinal layers. Furthermore, Liu et
al found that some children with various types of
amblyopia who had failed to achieve normal visual
acuity after treatment showed thickened RNFL in
the macular area with no fovea on OCT examination.31 Interestingly, Pang et al concluded that children who have amblyopia and unilateral high myopia tend to have a thicker fovea and thinner inner
and outer macula in the amblyopic eye compared
with the healthy fellow eye.32 Future studies are
warranted to determine whether the mechanism of
the macular changes is due to high myopia, amblyopia, or a combination of the two.
Many studies have demonstrated no difference
in the OCT-measured RNFL thickness in amblyopic
eyes compared with healthy fellow eyes of children
with strabismic amblyopia.30,33,34 Yen et al observed
a thicker RNFL in amblyopic eyes compared with
sound eyes of children with anisometropic amblyopia.33 Nevertheless, Al-Haddad et al and Repka et al
found no such difference.30,34
GLAUCOMA
Diagnosis and monitoring of glaucoma are more
difficult in children than adults because of the chal-
S21
Figure 1. Spectralis optical coherence tomography retinal nerve fiber layer (RNFL) map of the left eye of a 15-year-old girl with juvenile
glaucoma delineates the superotemporal and inferotemporal RNFL thinning.
lenges in obtaining reproducible and reliable IOPs
and visual fields in the pediatric population.35
Pediatric glaucoma is typically categorized by age of
onset into three types: congenital (infants younger than
3 months old), infantile (between 3 months and 3 years
of age), and juvenile (between 3 and 35 years of age).
Infants with congenital or infantile glaucoma are usually examined under anesthesia because of the technical difficulties encountered with using OCT in such a
noncompliant group of patients. Therefore, there is a
lack of OCT literature in congenital and infantile glaucoma, whereas many OCT studies have evaluated children with juvenile glaucoma. Figure 1 demonstrates the
Spectralis RNFL map of the left eye of a 15-year-old girl
with juvenile glaucoma and delineates the superotemporal and inferotemporal RNFL thinning.
Using Stratus OCT, children with juvenile glaucoma were found to have thinner RNFL and macula when compared to healthy peers.36 Furthermore,
RNFL and macular thickness declined with progression of glaucomatous damage.37 Those findings support the value of OCT in the early diagnosis and monitoring of pediatric glaucoma.
Retinopathy of prematurity (ROP) is characterized
by vasoproliferative retinopathy and occurs almost
exclusively in infants born prematurely. Maldonado
et al found cystoid macular edema (CME) in more
than half of the neonates with ROP by using handheld SD-OCT.38 Baker et al used OCT to study eyes
with ROP that had no significant macular pathology
on ophthalmoscopy and demonstrated subclinical
changes in foveal anatomy, including relative loss
of foveal depression, increased macular thickness,
and preservation of inner retinal layers within the
fovea.39 Macular abnormalities that are evident on
OCT, which are not always seen on ophthalmoscopy, may explain poor visual outcome in many of
these patients.
It has been hypothesized that macular edema in
eyes with severe ROP could be either a mechanical
traction exerted on the macula or a response to biochemical modulators, including higher concentrations of vascular endothelial growth factor (VEGF),
which could facilitate increased vascular permeability leading to retinal edema.38 In a study of 27 cytokines in the vitreous of 27 eyes of 19 infants with
stage 4 ROP, VEGF was found to have the strongest
correlation with vascular activity in the disease. Nevertheless, it is difficult to obtain vitreous samples
from infants with ROP to monitor the progression of
the disease.40 OCT provides a noninvasive alternative
with the ability to detect traction on the macula and
quantify macular edema. Future OCT studies should
focus on whether the OCT morphological findings
S22
Ophthalmic Surgery, Lasers & Imaging Retina | Healio.com/OSLIRetina
PEDIATRIC CHORIORETINAL VASCULAR DISEASE
Retinopathy of Prematurity
A
B
A
B
Figure 2. Fundus photograph (A) and optical coherence
tomography (OCT) image (B) of the right eye of a 4-year-old
girl with Coats’ disease. Fundus picture reveals dilated and
telangiectatic blood vessels with exudation and severe lipid
deposition in the macula. Longstanding submacular exudates
stimulated in-growth of fibrous tissue or blood vessels,
which lead to retinal pigment epithelial (RPE) migration and
hyperplasia, the formation of RPE detachment seen on OCT.
Intraretinal fluid collection is noted as well.
can serve as a useful predictor of future visual acuity
and development of visual pathway and cortical mapping. Measurement of choroidal thickness using OCT
may also be of interest.
Coats’ Disease
Coats’ disease is an idiopathic disease characterized by vascular abnormalities of the retina. It typically presents as telangiectatic and aneurysmal retinal
blood vessels associated with subretinal and intraretinal exudation and often subtotal or total exudative
retinal detachment (Figures 2 and 3).41 Kaul et al used
OCT to quantify the resolution of CME in a 16-yearold boy with Coats’ disease after intravitreal injection
with anti-VEGF (pegaptanib sodium).42 Using OCT,
the absence of vitreoretinal traction was confirmed in
November/December 2013 · Vol. 44, No. 6 (Suppl)
C
Figure 3. Fundus photograph (A), optical coherence tomography
(OCT) generated fundus image (B), and OCT image (C) of the
right eye of a 16-year-old girl with Coats’ disease. Fundus picture
reveals exudation and severe lipid deposition in the macula. OCT
shows retinal pigment epithelial migration and hyperplasia, and the
formation of fibrous scars.
a full thickness macular hole encountered in a 9-yearold boy with Coats’ disease.43 Hence, the chronic
macular exudation from telangiectatic vessels in the
setting of Coats’ disease could have caused cystoid
degeneration of the inner retinal layers and resulted
in a full-thickness macular hole.
S23
Figure 4. Fundus photograph and
optical coherence tomography
(OCT) image of the left eye of an
8-year-old boy with oculocutaneous
albinism. Note the hypopigmented
fundus. OCT demonstrated the
persistence of an abnormal highly
reflective band across the fovea,
multiple inner retinal layers normally
absent at the center of the fovea,
and loss of the normally thickened
photoreceptor nuclear layer usually
encountered at the fovea.
Choroidal Neovascularization
Shaken-Baby Syndrome
Kohly et al reported the results of pediatric
choroidal neovascular membranes secondary to a
variety of etiologies treated with intravitreal antiVEGF agents. Progress was monitored by clinical
exam, OCT, and fluorescein angiography. By using
OCT, they were able to quantitatively prove that
anti-VEGF agents were effective in the treatment of
pediatric choroidal neovascular membranes in this
case series.44
Shaken-baby syndrome is an important complication of child abuse. It is most common in children
younger than 3 years old. It has been reported that
30% to 40% of children subjected to child abuse
will have ophthalmic sequelae.48
Hand-held SD-OCT can provide invaluable
high-resolution imaging of the vitreoretinal interface and retina in infants with shaken-baby syndrome and reveal vitreoretinal abnormalities not
easily detected on clinical examination that may
be indicative of poor visual outcome.49,50 The most
frequent OCT findings in shaken-baby syndrome
were preretinal and multilayered retinal hemorrhages, perimacular folds, focal posterior vitreous
separation with multilayered hemorrhagic retinoschisis, disruption of the foveal architecture, and
foveolar detachment.48-51 Those OCT findings supported the pathophysiological theory of a direct
mechanical effect caused by preretinal blood accumulation, localized vitreous detachment, and
vitreoretinal traction.
Toxoplasmosis
Ocular toxoplasmosis results from retinal infection with the Apicomplexan protozoan Toxoplasma
gondii. Toxoplasmic retinochoroiditis is the most
common form of posterior uveitis in many countries.45 The infection can be congenital or acquired.
Toxoplasma retinochoroiditis typically affects the
posterior pole, and the lesions can be solitary,
multiple or satellite to a pigmented retinal scar.
Active lesions present as grey-white focus of retinal necrosis with adjacent choroiditis, vasculitis,
hemorrhage, and vitritis. The prognosis of ocular
toxoplasmosis is usually good in immunocompetent individuals, as long as the central macula is
not directly involved.46
Garg et al used OCT to document the appearance
of macular toxoplasmosis scars in 13 eyes of 10
consecutive patients (average age: 13 years).47 OCT
features included retinal thinning, retinal pigment
epithelial hyper-reflectivity, excavation, intraretinal cysts, and fibrosis. In patients with better than
expected visual acuity, parafoveal lesions or an intact neurosensory layer were seen on OCT.
S24
INHERITED RETINAL DISORDERS
Albinism
SD-OCT has been used to study the spectrum
of foveal architecture in pediatric albinism and
clarify the morphology of foveal hypoplasia seen
clinically in ocular albinism (Figure 4). 52 Some of
the abnormalities noted on OCT were the persistence of an abnormal highly reflective band across
the fovea, multiple inner retinal layers normally
absent at the center of the fovea, and loss of the
Ophthalmic Surgery, Lasers & Imaging Retina | Healio.com/OSLIRetina
A
B
Figure 5. Cirrus high-definition optical coherence tomography (OCT) generated fundus image (A), and OCT image (B) of the right eye of
a 9-year-old boy with Best’s disease: Yolk-like (vitelliform) lesion is noted in the central macula.
Figure 6. Optical coherence
tomography (OCT) image of the
right eye of a 12-year-old girl with
inherited retinal dystrophy. OCT
demonstrated macular edema
and delineated the hyporeflective
cystoid spaces within the central
macula.
normally thickened photoreceptor nuclear layer
usually encountered at the fovea. The optic nerve
was also elevated in multiple eyes of individuals
with ocular albinism.52
Leber Congenital Amaurosis
Leber congenital amaurosis is an autosomal recessive inherited retinal degenerative disorder that
causes an infant to be born with severely impaired
vision. Photoreceptors are lost across a wide region
of human central retina as early as the first decade
of life in children with the disorder.53 Assessment
of visual function is often difficult in infants, leading to a prominent role for electrodiagnostic testing
such as electroretinography. OCT may function as
an objective diagnostic tool by detecting foveal and
extrafoveal photoreceptor loss early in the course
of Leber congenital amaurosis. Differences in the
topography of residual photoreceptors suggest that
it may be advisable to use individualized outer nuclear layer mapping to guide the location of subretinal injections for gene therapy and thereby maximize the potential for efficacy.54
November/December 2013 · Vol. 44, No. 6 (Suppl)
Best’s Disease
Best’s disease is an autosomal dominant inherited
type of macular dystrophy. It is identified by a large
yellow yolk-like (vitelliform) lesion in the central
macula. OCT can help define the characteristics of
this “egg yolk” appearance (Figure 5).
Furthermore, OCT has the ability to visualize
CME that is associated with inherited retinal dystrophies (Figure 6).
UVEITIS
The majority of pediatric uveitis cases are idiopathic. Nevertheless, etiological factors can be ascertained in some cases, with juvenile idiopathic
arthritis accounting for approximately 75% of all
pediatric anterior uveitis.55,56 In a study of macular
morphology and retinal complications of juvenile
idiopathic arthritis–related uveitis in 24 eyes of
14 children, Stratus OCT was able to detect macular edema in 25% of the eyes, most of which was
mild and not clinically evident.57 Because macular
involvement could be underestimated by a traditional clinical examination, OCT might provide an
S25
Figure 7. Optical coherence
tomography (OCT) image of the
left eye of an 11-year-old boy
with intermediate uveitis. OCT
demonstrated cystoid macular
edema
and
delineated
the
hyporeflective cystoid spaces within
the inner retinal layers.
additional diagnostic tool with much higher sensitivity for detecting maculopathy as a significant
complication of uveitis in children with juvenile
idiopathic arthritis. Figure 7 shows OCT imaging
of CME in the left eye of an 11-year-old boy with
intermediate uveitis.
OPTIC NERVE HEAD ANOMALIES
OCT has been proven to measure the peripapillary RNFL thickness with excellent reproducibility,58 and its role in the diagnosis and monitoring
of various optic nerve head anomalies has grown
in the pediatric population. In comparison with
healthy controls, an increased RNFL thickness was
observed in children with pseudotumor cerebri,59
whereas RNFL measured thinner in the affected
eyes of children with multiple sclerosis, acute disseminated encephalomyelitis, and optic neuritis.60
TUMORS
diagnose OPGs in children. Using Stratus OCT,
Chang et al63 found that NF1 subjects with OPGs
had thinner RNFL (61 μm) and smaller macular volume (6.2 mm3) when compared with age-matched
healthy control subjects (108 μm, 6.8 mm3) (P < .01).
NF1 subjects without OPGs have equivalent RNFL
thickness and macular volume as matched healthy
control subjects. Therefore, OCT could be used as
a noninvasive screening tool to determine the possibility of an OPG, thereby avoiding expensive MRI
and possible risks of anesthesia in young children.
OCT data can augment neuroimaging findings in
children with NF1 with suspected or known OPGs
when correlated with clinical examinations and
visual field test findings. Critical OCT changes in
RNFL and macular thicknesses can establish appropriate treatment timing in children with NF1 with
vision-threatening OPGs.
Using AS-OCT (Visante OCT 3.0; Carl Zeiss
Meditec, Dublin, CA) in 200 eyes (including children), anterior segment tumors involving the iris
stroma, ciliary body, iris pigment epithelium, conjunctiva, and sclera were imaged and compared to
ultrasound biomicroscopy (OPKO Instrumentation/
OTI, Miami, FL). Ultrasound biomicroscopy provided superior visualization of the posterior margin
and entire tumor configuration.64
OCT is more sensitive than clinical examination and ultrasonography in the detection of retinal
thinning, cystoid and non-cystoid macular edema,
subfoveal fluid, and surface wrinkling maculopathy.61 However, ultrasonography is more sensitive
in detection of posterior vitreous detachment. 61
Shields et al used OCT in the evaluation of pediatric fundus lesions in retinal capillary hemangioma,
astrocytic hamartoma, and retinoblastoma.61
Neurofibromatosis type 1 (NF1) is the most common neurocutaneous disorder, with an approximate
incidence of one in 3,500.62 Optic pathway gliomas
(OPG) develop in 15% of individuals with NF1,
commonly in childhood, and are associated with
significant visual risks. OPGs are difficult to detect
via clinical inspection in children, often requiring magnetic resonance imaging. Therefore, there
is a need for improved noninvasive techniques to
Using Visante OCT, Bailey et al reported thicker
ciliary body measurements with myopia and a longer axial length in children 8 to 15 years of age.65
This AS-OCT finding contradicted the choroidal expansion theory and raised the possibility that there
is a physiological response of the ciliary body in
myopia rather than simple mechanical stretching.
Chow et al reported a case of secondary congenital aphakia diagnosed by using AS-OCT in a
S26
Ophthalmic Surgery, Lasers & Imaging Retina | Healio.com/OSLIRetina
MISCELLANEOUS
Figure 8. Optical coherence
tomgoraphy image of the left eye
in a 12-year-old girl with aniridia
showing foveal hypoplasia and loss
of the foveal depression seen in
healthy individuals.
CONCLUSION
Figure 9. Wide-field swept-source optical coherence tomography
(SS-OCT) image of the right eye of a healthy 25-year-old man.
SS-OCT has the advantages of providing wide-field view and
augmenting visualization of the choroids.
7-year-old boy with nystagmus.66 AS-OCT was of
significant prognostic and management value, because it provided high-resolution images of the
anterior segment and revealed the presence of lens
capsules. The child later benefited from bilateral
sulcus-fixated IOL implantation surgery.
Intraoperative OCT confirmed the diagnosis of
bilateral macular colobomata in a 3-year-old girl
with Down syndrome.67
Congenital aniridia is a heritable disease characterized by an obvious iris defect, small cornea,
small disc, decreased visual acuity with nystagmus, cataract, and foveal hypoplasia (Figure 8).
November/December 2013 · Vol. 44, No. 6 (Suppl)
The current generation of OCT technology is
based on spectral-domain image acquisition. This
involves the use of a spectrometer and a mathematical (Fourier) transformation to generate OCT
A-scans as a function of frequency. The next generation of commercial OCT devices is likely to use
swept-source technology to generate OCT images.
With this approach, a tunable laser is used to generate OCT A-scans as a function of frequency. Sweptsource OCT devices will allow further increases in
image acquisition speed.68 For example, DRI OCT1 (Topcon, Tokyo, Japan) will allow acquisition of
approximately 100,000 A-scans per second. In fact,
research prototypes using swept-source lasers are
even faster, with some devices allowing millions of
A-scans to be generated per second. This greatly enhanced image acquisition speed will be of particular
interest for pediatric populations as it may facilitate
wide-field imaging of the fundus, greatly enhancing
visualization of extramacular pathologies. Sweptsource devices will also employ long-wavelength
OCT light sources, which will greatly augment visualization of the choroid (Figure 9).69 Longitudinal
measurements of the choroid may be of particular
interest in children because the results from animal
studies suggest an important role for this structure
in ocular development.70 Greater OCT image acquisition speeds will also facilitate the development of
“optical coherence angiography,” the use of OCT to
provide noninvasive mapping of the retinal and/or
choroidal microvasculature (this technique is also
commonly referred to as “phase contrast” or “phase
variance” OCT).68 With the exponential growth of
these technologies, and their noninvasive nature, it
seems clear that the use of OCT in pediatric populations is likely to increase greatly in the coming
years, aiding clinical decision making and providing
new insights into pediatric disease pathophysiology.
S27
REFERENCES
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
S28
CATT Research Group, Martin DF, Maguire MG et al.
Ranibizumab and bevacizumab for neovascular age-related
macular degeneration. N Engl J Med. 2011;364(20):1897-1908.
Nguyen QD, Brown DM, Marcus DM et al. Ranibizumab for
diabetic macular edema: results from 2 phase III randomized
trials: RISE and RIDE. Ophthalmology. 2012;119(4):789-801.
Keane PA, Sadda SR. Imaging chorioretinal vascular disease. Eye
(Lond). 2010;24(3):422-427.
Kiernan DF, Mieler WF, Hariprasad SM. Spectral-domain optical
coherence tomography: a comparison of modern high-resolution
retinal imaging systems. Am J Ophthalmol. 2010;149(1):18-31.
Hammer DX, Ferguson RD, Magill JC, White MA, Elsner AE,
Webb RH. Compact scanning laser ophthalmoscope with highspeed retinal tracker. Appl Opt. 2003;42(22):4621-4632.
Hammer DX, Ferguson RD, Magill JC, et al. Active retinal
tracker for clinical optical coherence tomography systems. J
Biomed Opt. 2005;10(2):024038.
Vinekar A, Sivakumar M, Shetty R et al. A novel technique using
spectral-domain optical coherence tomography (Spectralis, SDOCT+HRA) to image supine non-anaesthetized infants: utility
demonstrated in aggressive posterior retinopathy of prematurity.
Eye (Lond). 2010;24(2):379-382.
Jung W, Kim J, Jeon M, Chaney EJ, Stewart CN, Boppart SA.
Handheld optical coherence tomography scanner for primary
care diagnostics. IEEE Trans Biomed Eng. 2011;58(3):741-744.
Ray R, Barañano DE, Fortun JA, Schwent BJ, Cribbs BE,
Bergstrom CS, Hubbard GB 3rd, Srivastava SK. Intraoperative
microscope-mounted spectral domain optical coherence
tomography for evaluation of retinal anatomy during macular
surgery. Ophthalmology. 2011;118(11):2212-2217.
Tao YK, Ehlers JP, Toth CA, Izatt JA. Intraoperative spectral
domain optical coherence tomography for vitreoretinal surgery.
Opt Lett. 2010;35(20):3315-3317.
Chow VW, Wong AL, Fan DS. Use of anterior segment OCT in
the evaluation and management of congenital aphakia. J Pediatr
Ophthalmol Strabismus. 2009.
Samarawickrama C, Wang JJ, Huynh SC, et al. Ethnic differences
in optic nerve head and retinal nerve fiber layer thickness
parameters in children. Br J Ophthalmol. 2010;94(7):871-876.
El-Dairi MA, Asrani SG, Enyedi LB, Freedman SF. Optical
coherence tomography in the eyes of normal children. Arch
Ophthalmol. 2009;127(1):50-58.
Leung MM, Huang RY, Lam AK. Retinal nerve fiber layer thickness
in normal Hong Kong chinese children measured with optical
coherence tomography. J Glaucoma. 2010;19(2):95-99.
Salchow DJ, Oleynikov YS, Chiang MF, et al. Retinal nerve
fiber layer thickness in normal children measured with optical
coherence tomography. Ophthalmology. 2006;113(5):786-791.
Ahn HC, Son HW, Kim JS, Lee JH. Quantitative analysis of
retinal nerve fiber layer thickness of normal children and
adolescents. Korean J Ophthalmol. 2005;19(3):195-200.
Hougaard JL, Ostenfeld C, Heijl A, Bengtsson B. Modelling the
normal retinal nerve fiber layer thickness as measured by Stratus
optical coherence tomography. Graefes Arch Clin Exp Ophthalmol.
2006;244(12):1607-1614.
Sehi M, Ume S, Greenfield DS. Scanning laser polarimetry
with enhanced corneal compensation and optical coherence
tomography in normal and glaucomatous eyes. Invest Ophthalmol
Vis Sci. 2007;48(5):2099-2104.
Lu AT, Wang M, Varma R, et al. Combining nerve fiber layer
parameters to optimize glaucoma diagnosis with optical coherence
tomography. Ophthalmology. 2008;115(8):1352-1357.
Budenz DL, Anderson DR, Varma R, et al. Determinants of
normal retinal nerve fiber layer thickness measured by Stratus
OCT. Ophthalmology. 2007;114(6):1046-1052.
Varma R, Bazzaz S, Lai M. Optical tomography-measured retinal
nerve fiber layer thickness in normal latinos. Invest Ophthalmol
Vis Sci. 2003;44(8):3369-3373.
Nagai-Kusuhara A, Nakamura M, Fujioka M, Tatsumi Y, Negi
A. Association of retinal nerve fiber layer thickness measured by
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
confocal scanning laser ophthalmoscopy and optical coherence
tomography with disc size and axial length. Br J Ophthalmol.
2008;92(2):186-190.
Qian J, Wang W, Zhang X, et al. Optical coherence tomography
measurements of retinal nerve fiber layer thickness in chinese
children and teenagers. J Glaucoma. 2011;20(8):509-513.
Turk A, Ceylan OM, Arici C. Evaluation of the nerve fiber
layer and macula in the eyes of healthy children using spectraldomain optical coherence tomography. Am J Ophthalmol.
2012;153(3):552-559.
Tsai DC, Huang N, Hwu JJ, Jueng RN, Chou P. Estimating
retinal nerve fiber layer thickness in normal schoolchildren with
spectral-domain optical coherence tomography. Jpn J Ophthalmol.
2012;56(4):362-370.
Bendschneider D, Tornow RP, Horn FK, et al. Retinal nerve fiber
layer thickness in normals measured by spectral domain OCT. J
Glaucoma. 2010;19(7):475-482.
Hirasawa H, Tomidokoro A, Araie M, et al. Peripapillary retinal
nerve fiber layer thickness determined by spectral domain optical
coherence tomography in ophthalmologically normal eyes. Arch
Ophthalmol. 2010;128(11):1420-1426.
Alasil T, Wang K, Keane PA, et al. Analysis of Normal Retinal
Nerve Fiber Layer Thickness by Age, Sex, and Race Using
Spectral Domain Optical Coherence Tomography. J Glaucoma.
2012.
The Eye MD Association. Pediatric Ophthalmology and
Strabismus. San Francisco: American Academy of Ophthalmology.
2006;67-75.
Al-Haddad CE, Mollayess GM, Cherfan CG, Jaafar DF, Bashshur
ZF. Retinal nerve fiber layer and macular thickness in amblyopia
as measured by spectral-domain optical coherence tomography.
Br J Ophthalmol. 2011;95(12):1696-1699.
Liu H, Zhong L, Zhou X, Jin QZ. Macular abnormality observed
by OCT in children with amblyopia failing to achieve normal
visual acuity after long-term treatment. J Pediatr Ophthalmol
Strabismus. 2010;47(1):17-23.
Pang Y, Goodfellow GW, Allison C, Block S, Frantz KA. A
prospective study of macular thickness in amblyopic children
with unilateral high myopia. Invest Ophthalmol Vis Sci.
2011;52(5):2444-2449.
Yen MY, Cheng CY, Wang AG. Retinal nerve fiber layer
thickness in unilateral amblyopia. Invest Ophthalmol Vis Sci.
2004;45(7):2224-2230.
Repka MX, Goldenberg-Cohen N, Edwards AR. Retinal nerve
fiber layer thickness in amblyopic eyes. Am J Ophthalmol.
2006;142(2):247-251.
El-Dairi MA, Asrani SG, Enyedi LB, Freedman SF. Optical
coherence tomography in the eyes of normal children. Arch
Ophthalmol. 2009;127(1):50-58.
Hess DB, Asrani SG, Bhide MG, Enyedi LB, Stinnett SS,
Freedman SF. Macular and retinal nerve fiber layer analysis
of normal and glaucomatous eyes in children using optical
coherence tomography. Am J Ophthalmol. 2005;139(3):509-517.
El-Dairi MA, Holgado S, Asrani SG, Enyedi LB, Freedman
SF. Correlation between optical coherence tomography and
glaucomatous optic nerve head damage in children. Br J
Ophthalmol. 2009;93(10):1325-1330.
Maldonado RS, O’Connell RV, Sarin N et al. Dynamics of
human foveal development after premature birth. Ophthalmology.
2011;118(12):2315-2325.
Baker PS, Tasman W. Optical coherence tomography imaging of
the fovea in retinopathy of prematurity. Ophthalmic Surg Lasers
Imaging. 2010;41(2):201-206.
Sato T, Kusaka S, Shimojo H, Fujikado T. Simultaneous analyses
of vitreous levels of 27 cytokines in eyes with retinopathy of
prematurity. Ophthalmology. 2009;116(11):2165-2169.
Shields JA, Shields CL. Review: Coats disease: the 2001 LuEsther
T. Mertz lecture. Retina. 2002;22(1):80-91.
Kaul S, Uparkar M, Mody K, Walinjkar J, Kothari M, Natarajan
S. Intravitreal anti-vascular endothelial growth factor agents as an
adjunct in the management of Coats’ disease in children. Indian J
Ophthalmol. 2010;58(1):76-78.
Ophthalmic Surgery, Lasers & Imaging Retina | Healio.com/OSLIRetina
43. Kumar V, Goel N, Ghosh B, Raina UK. Full-thickness macular
hole and macular telangiectasia in a child with Coats’ disease.
Ophthalmic Surg Lasers Imaging. 2010;4:e1-3.
44. Kohly RP, Muni RH, Kertes PJ, Lam WC. Management of
pediatric choroidal neovascular membranes with intravitreal
anti-VEGF agents: a retrospective consecutive case series. Can J
Ophthalmol. 2011 Feb;46(1):46-50.
45. Furtado JM, Winthrop KL, Butler NJ, Smith JR. Ocular
toxoplasmosis I: parasitology, epidemiology and public health.
Clin Experiment Ophthalmol. 2012;41(1)82-94.
46. Bonfioli AA, Orefice F. Toxoplasmosis. Semin Ophthalmol.
2005;20(3):129-141.
47. Garg S, Mets MB, Bearelly S, Mets R. Imaging of congenital
toxoplasmosis macular scars with optical coherence tomography.
Retina. 2009;29(5):631-637.
48. Sturm V, Landau K, Menke MN. Optical coherence tomography
findings in Shaken Baby syndrome. Am J Ophthalmol.
2008;146(3):363-368.
49. Koozekanani DD, Weinberg DV, Dubis AM, Beringer J,
Carroll J. Hemorrhagic Retinoschisis in Shaken Baby Syndrome
Imaged with Spectral Domain Optical Coherence Tomography.
Ophthalmic Surg Lasers Imaging. 2010;1-3.
50. Muni RH, Kohly RP, Charonis AC, Lee TC. Retinoschisis detected
with handheld spectral-domain optical coherence tomography
in neonates with advanced retinopathy of prematurity. Arch
Ophthalmol. 2010;128(1):57-62.
51. Scott AW, Farsiu S, Enyedi LB, Wallace DK, Toth CA. Imaging the
infant retina with a hand-held spectral-domain optical coherence
tomography device. Am J Ophthalmol. 2009;147(2):364-373.
52. Chong GT, Farsiu S, Freedman SF, et al. Abnormal foveal
morphology in ocular albinism imaged with spectral-domain
optical coherence tomography. Arch Ophthalmol. 2009;127(1):3744.
53. Bainbridge JW, Smith AJ, Barker SS, et al. Effect of gene therapy
on visual function in Leber’s congenital amaurosis. N Engl J Med.
2008;358(21):2231-2239.
54. Jacobson SG, Cideciyan AV, Aleman TS, et al. Photoreceptor layer
topography in children with leber congenital amaurosis caused by
RPE65 mutations. Invest Ophthalmol Vis Sci. 2008;49(10):45734577.
55. Foster CS. Diagnosis and treatment of juvenile idiopathic arthritisassociated uveitis. Curr Opin Ophthalmol. 2003;14(6):395-398.
56. Levy-Clarke GA, Nussenblatt RB, Smith JA. Management of chronic
pediatric uveitis. Curr Opin Ophthalmol. 2005;16(5):281-288.
November/December 2013 · Vol. 44, No. 6 (Suppl)
57. Paroli MP, Spinucci G, Fabiani C, Pivetti-Pezzi P. Retinal
complications of juvenile idiopathic arthritis-related uveitis: a
microperimetry and optical coherence tomography study. Ocul
Immunol Inflamm. 2010;18(1):54-59.
58. Wu H, de Boer JF, Chen TC. Diagnostic capability of spectraldomain optical coherence tomography for glaucoma. Am J
Ophthalmol. 2012;153(5):815-826.
59. El-Dairi MA, Holgado S, O’Donnell T, Buckley EG, Asrani
S, Freedman SF. Optical coherence tomography as a tool
for monitoring pediatric pseudotumor cerebri. J AAPOS.
2007;11(6):564-570.
60. Yeh EA, Weinstock-Guttman B, Lincoff N, et al. Retinal nerve
fiber thickness in inflammatory demyelinating diseases of
childhood onset. Mult Scler. 2009;15(7):802-810.
61. Shields CL, Mashayekhi A, Luo CK, Materin MA, Shields JA.
Optical coherence tomography in children: analysis of 44 eyes
with intraocular tumors and simulating conditions. J Pediatr
Ophthalmol Strabismus. 2004;41(6):338-344.
62. Listernick R, Ferner RE, Liu GT, Gutmann DH. Optic
pathway gliomas in neurofibromatosis-1: Controversies and
recommendations. Ann Neurol. 2007;61(3):189-198.
63. Chang L, El-Dairi MA, Frempong TA, et al. Optical coherence
tomography in the evaluation of neurofibromatosis type-1 subjects
with optic pathway gliomas. J AAPOS. 2010;14(6):511-517.
64. Bianciotto C, Shields CL, Guzman JM, et al. Assessment of
anterior segment tumors with ultrasound biomicroscopy versus
anterior segment optical coherence tomography in 200 cases.
Ophthalmology. 2011;118(7):1297-1302.
65. Bailey MD, Sinnott LT, Mutti DO. Ciliary body thickness
and refractive error in children. Invest Ophthalmol Vis Sci.
2008;49(10):4353-4360.
66. Chow VW, Wong AL, Fan DS. Use of anterior segment OCT in
the evaluation and management of congenital aphakia. J Pediatr
Ophthalmol Strabismus. 2009:1-2.
67. Aziz HA, Ruggeri M, Berrocal AM. Intraoperative OCT of
bilateral macular coloboma in a child with Down syndrome. J
Pediatr Ophthalmol Strabismus. 2011;48:e37-39.
68. Drexler W, Fujimoto JG. State-of-the-art retinal optical
coherence tomography. Prog Retin Eye Res. 2008;27(1):45-88.
69. Keane PA, Ruiz-Garcia H, Sadda SR. Clinical applications of
long-wavelength (1,000-nm) optical coherence tomography.
Ophthalmic Surg Lasers Imaging. 2011;42 Suppl:S67-74.
70. Nickla DL, Wallman J. The multifunctional choroid. Prog Retin
Eye Res. 2010;29(2):144-168.
S29