Paediatric Electrophysiology: A Practical Approach 9

Graham E. Holder, Anthony G. Robson

| Core Messages A formal clinical audit of the role of electro-

∑ Electrophysiological testing provides physiology in paediatric practice demonstrated
an objective and noninvasive method a significant influence on management [88].
for visual pathway evaluation After an initial description of the available tech-
∑ Complementary use of different electro- niques and their uses, the subsequent discus-
physiological procedures allows accurate sion will adopt a practical approach to diagno-
characterisation and localisation of dys- sis, based on presenting signs and symptoms,
function. EOG: The photoreceptor/RPE to demonstrate how electrophysiological testing
interface; ERG: rod and cone photoreceptor can enable management decisions to be taken
and inner retinal function; PERG: macular with greater confidence.
and retinal ganglion cell function; VEP:
intracranial visual pathway function
∑ Electrophysiology enables distinction 9.2
between disorders that may present with Electrophysiological Techniques
similar signs and/or symptoms and facili-
tates differentiation between benign and 9.2.1
severe, progressive and stationary disorders Electroretinography
∑ Invaluable in suspected nonorganic visual
loss The electroretinogram (ERG) is the mass re-
∑ Accurate electrophysiological phenotyping sponse of the retina to a luminance stimulus,
is likely to become increasingly important usually a stroboscopically generated short-
as genotyping increases and new therapies duration flash (Fig. 9.1). In adults, ERGs are
are developed recorded using corneal electrodes with stimuli
delivered via a Ganzfeld bowl. This approach is
tenable with older children who are capable of
understanding the demands of testing, but
there are two distinct schools of thought in rela-
9.1 tion to the young child or infant. Some adopt the
Introduction approach that children are simply young adults,
and use the same techniques; inevitably this
The electrophysiological examination of the requires either restraint or sedation in some pa-
paediatric patient can be of great clinical im- tients. Others adopt the view that the clinical
portance. In addition to the objective nature of data required in a young child are different to
the data provided by electrophysiological test- those in an adult population, requiring answers
ing, the potential inability of a child to describe to different, less complex questions, such as “is
accurately, if at all, their symptoms places elec- this baby blind” or “why has this child got nys-
trophysiology in a privileged position of diag- tagmus”, and that clinically meaningful and sat-
nostic importance. Further, it is noninvasive. isfactory data can be obtained using less inva-
134 Chapter 9 Paediatric Electrophysiology: A Practical Approach

Fig. 9.1. Examples of normal pattern ERG, full-field ERGs, ON-OFF ERGs and S-cone specific ERGs. Major
components are labelled. The ON-OFF ERG is recorded to 200 ms orange stimulation with a green photopic
background. Normal pattern and flash VEPs are also shown

sive techniques, particularly involving the use a-wave, is known as a negative or electronega-
of surface recording electrodes [47, 60]. The tive ERG. A negative ERG does not mean that
authors’ approach is to adapt procedures ac- the ERG is undetectable, merely that the wave-
cording to the ability of the patient to cooperate, form is dominated by the negative a-wave, and
using a simplified protocol and surface elec- as such indicates inner retinal dysfunction.
trodes in young children and introducing Under photopic conditions, there is a probable
longer procedures, Ganzfeld stimulation, contribution from post-receptoral structures to
corneal electrodes and mydriasis in those chil- the a-wave, particularly at low luminance levels
dren who are able to tolerate longer, more de- [15, 76].
manding protocols. The theoretical discussion Much clinical ERG work is based on the
that follows on the origins of the different ERG Standards and recommendations of the Inter-
components is unaffected by such considera- national Society for Clinical Electrophysiology
tions. of Vision (ISCEV). The ISCEV Standard for ERG
The ERG to a bright flash in a dark-adapted recording [57] defines a standard flash of 1.5–
eye consists of two main components, the nega- 3.0 cd.s.m–2. A response specific for the rod sys-
tive a-wave and the positive b-wave (Fig. 9.1). tem is obtained using the standard flash attenu-
Approximately the first 10 ms of the a-wave re- ated by 2.5 log units in a dark-adapted eye. Dark
flects photoreceptor hyperpolarisation, and in adaptation, to comply with the ISCEV Standard,
general, marked a-wave amplitude reduction requires at least 20 min in complete darkness
reflects photoreceptor loss or dysfunction. The and maximum mydriasis. The response to the
b-wave, which should be of higher amplitude, standard flash under dark adaptation is a mixed
reflects retinal activity generated post-photo- rod–cone response dominated by rod function.
transduction, predominantly in relation to de- Commencing with the most recent Standard
polarisation of the ON- bipolar cells [76]. An document, ISCEV also suggests the recording
ERG waveform in which the a-wave is spared, of a response to a higher intensity flash
but the b-wave shows selective reduction, often (~11.0 cd.s.m–2) better to record the a-wave, and
such that it is of lower amplitude than the thus photoreceptor function. This can be partic-
 9.2 Electrophysiological Techniques 135

ularly helpful in the young child. Photopic the presence or absence of subtle rod system
ERGs, in addition to a single flash cone response dysfunction is not usually of clinical relevance
(with a rod-suppressing background and ade- in a young infant. Mydriasis is not usually used
quate photopic adaptation), are also recorded to in infants, as the act of instilling mydriatic drops
a 30-Hz flicker stimulus (Fig. 9.1); rods have is often sufficient to cause undesired distress.
poor temporal resolution and do not contribute Childhood ERGs are often prone to the
significantly to the response at this stimulus effects of eye movement and eye closure and it
rate. The ERG is a mass response, and is normal is important to demonstrate reproducibility. It
when dysfunction is confined to small retinal is also important to relate the ERGs obtained to
areas. Despite the high photoreceptor density, the age of the child; the maturation of ERGs in
this also applies to macular dysfunction; an eye early and late infancy has been extensively and
with dysfunction confined to the macula does recently reviewed [28, 86].
not have a significantly abnormal ERG. Separa-
tion of the cone ON (depolarising bipolar cells,
DBCs) and OFF (hyperpolarising bipolar cells, 9.2.2
HBCs) responses can be performed using long Pattern Electroretinography
duration stimulation with a photopic back-
ground [77], using either a shutter system or The pattern electroretinogram (PERG) is the re-
light emitting diodes to produce the stimulus. sponse of central retina and is usually measured
The above-mentioned techniques can be using a reversing black and white checker-
used in older children. The approach to infants board. It is important that there is no luminance
adopted in the authors’ laboratories differs. The change during pattern reversal. It allows both a
initial recordings, using surface recording elec- measure of central retinal function and, in rela-
trodes on the lower eyelids with reference to tion to its origins, an evaluation of retinal
electrodes at the ipsilateral outer canthi, take ganglion cell function. It is thus of great value in
place under light-adapted conditions and in- the electrophysiological differentiation between
clude the ERGs to single flash and flicker. These macular dysfunction and generalised retinal
determine the presence or absence of cone sys- dysfunction or optic nerve dysfunction in the
tem function, with the implicit time of the flick- older child with visual acuity loss (see [40] for a
er ERG being a particularly good indicator of comprehensive review). It is important to pre-
generalised cone system function. The child is serve the optics of the eye for PERG recording,
then dark adapted for 5 min, and bright flash which requires non-contact lens electrodes in
stimuli given. These should evoke ERGs of very contact with the cornea or bulbar conjunctiva to
different waveform and much higher amplitude preserve the optics of the eye, and no mydriasis.
than the responses to single flashes under light- The gold foil, the DTL and the H-K loop elec-
adapted conditions and allow an estimation of trode are all suitable. Ipsilateral outer canthus
whether there is a functioning scotopic system. reference electrodes are mandatory; there is
For the young infant, the clinical questions are contamination from the cortically generated
generally (a) is there an ERG? (b) is there gener- VEP if forehead or ear “reference” electrodes are
alised cone dysfunction? (c) is there a function- used [7]. In young children incapable of tolerat-
ing scotopic system? (d) is there an electronega- ing corneal electrodes, surface electrodes may
tive ERG? These questions can adequately be be used [14]. The signal:noise ratio is inevitably
answered by such recordings. Typical examples lower compared with corneal recordings and
of surface recordings are illustrated in Fig. 9.2. responses are particularly sensitive to alter-
Throughout these recordings, the child is usual- ations in fixation. Continuous monitoring and
ly sitting on the lap of the mother, and stimula- “interrupted averaging” [40, 72] during lapses
tion is applied using a hand-held stroboscopic in fixation or to allow blinking is essential in
flash. If the child remains content after 5 min order to optimise the quality of recordings. Sur-
dark adaptation, further recordings, perhaps face PERGs may be elicited using large stimulus
using rod-specific stimulation, can be used, but fields; the use of such stimuli may be beneficial
136 Chapter 9 Paediatric Electrophysiology: A Practical Approach

in terms of signal:noise ratio and by encourag- ground electroencephalographic activity, and

ing better fixation, but require cautious inter- computerised signal averaging and repetitive
pretation and comparison with corresponding stimulation are used to extract the time-locked
normal values. In general, the presence of any VEP. A reversing black and white checkerboard
PERG excludes severe macular dysfunction. or diffuse flash stimulation is commonly used,
There are two main components in the so- but pattern onset/offset is effective in certain
called transient PERG: P50 at approximately conditions (see below) and is less dependent on
50 ms and a larger N95 at 95 ms [37] (Fig. 9.1). stable fixation. The checkerboard reversal VEP is
Assessment concentrates on the amplitude of usually the most sensitive indicator of optic
P50, measured from the trough of the small nerve dysfunction. Monocular stimulation is es-
early negative N35 component; the latency of sential and multi-channel recordings help locali-
P50 measured to peak; and the amplitude of sation of dysfunction. Infants and children often
N95, measured to trough from the peak of P50. require constant encouragement and reassur-
The N95 is a contrast-related component gener- ance and fixation and cooperation should be
ated in the retinal ganglion cells. Approximately continuously monitored; averaging may then be
70 % of P50 appears to be ganglion cell-related, suspended during periods of inattention.
but the remainder is not related to spiking cell The transient (<2/s recommended) checker-
function and may be generated more distally in board reversal VEP in adults contains a promi-
the retina [81]. The exact origins have yet to be nent positive component at approximately
ascertained. Although the PERG is generated in 100 ms known as P100 (Fig. 9.1). Stimulus pa-
inner retina, the P50 component is “driven” by rameters such as contrast, luminance, check
the macular photoreceptors and thus reflects size, field size, etc., are important determinants
macular function. of the waveform, and it is essential for each
For optimal recording of the PERG, an analy- laboratory to establish its age-matched normal
sis time of 150 ms or greater is usually used. It is controls. Maturational changes in pattern and
a low-amplitude signal and computerised aver- flash VEPs have been extensively documented
aging is essential. The necessary stringent tech- [12, 48, 71].
nical controls are important and are fully dis-
cussed elsewhere [25]. Binocular stimulation
and recording is usually preferred so the better 9.2.4
eye can maintain fixation and accommodation, Electro-oculography
but if there is a history of squint it is necessary to
use monocular recording. P50 is sensitive to op- The electro-oculogram (EOG) refers to meas-
tical blur, and accurate refraction is important. urement of the standing potential of the eye.
PERG amplitude is related almost linearly to This potential difference is generated across the
stimulus contrast at low stimulus frequencies. retinal pigment epithelium and manifests as a
ISCEV recommends a high-contrast black and dipole between the back of the eye and the elec-
white reversing checkerboard with approxi- tropositive cornea (for a recent review see [25]).
mately 50-min checks in a 10- to 16-degree field. The ERG is a global response and allows assess-
ment of the photoreceptor/RPE interface.A nor-
mal EOG depends on the integrity of the pho-
9.2.3 toreceptors and a functioning RPE. A reduced
Cortical Visual Evoked Potentials EOG is generally accompanied by a reduction in
the full-field ERG unless dysfunction is con-
Visual evoked potentials (VEPs) are used to fined to the RPE (see Sect. 9.6.1.2). The ISCEV-
assess the integrity and function of the visual standard EOG is measured by recording the
pathways, particularly the optic nerves and optic potentials generated by fixed excursion eye
chiasm. Responses are recorded using scalp elec- movements during a standard period of dark
trodes placed over the occipital areas. The VEP is adaptation, and then during restoration to full
a relatively small signal in relation to the back- photopic conditions [56]. The eye movement
 9.3 Investigation of Night Blindness 137

excursions are prompted by alternately flashing Typically patients present with night blindness
lights and accurate testing depends on the and visual field constriction. Central vision may
child’s cooperation and ability to follow these or may not be involved. Classical signs include
fixation lights; it is rarely possible to test chil- bone-spicule pigmentation, vessel attenuation
dren younger than about 6 years of age. The and disc pallor, but the fundus may be normal
EOG is usually expressed as a light peak:dark in the early stages of disease, and this is often
trough ratio, the Arden index. the case in young children. Fundus appearance
Accurate diagnosis and phenotyping of reti- may be a poor indicator of the severity of dys-
nal dystrophies often relies on the pattern of function.
electrophysiological abnormality. The pattern The rod-specific ERG, reflecting rod-system
ERG is used to assess central retinal function sensitivity, arises in the inner retina and is usu-
and the full-field ERG generalised retinal func- ally subnormal or undetectable in RP. The most
tion. Patients with generalised retinal dysfunc- direct ERG measure of rod photoreceptor func-
tion and severe ERG abnormalities can have tion is the a-wave of the bright flash (maximal)
normal PERGs if the macula is spared. Con- ERG and in RP this will also be affected with as-
versely, patients with disease confined to the sociated reduction of the b-wave (Fig. 9.3). The
macula have normal ERGs, but the PERG P50 normal maximal ERG is of high amplitude,
may be profoundly abnormal. Thus, optimal usually allowing easy recording. This can be
phenotyping requires the use of both tech- exploited in paediatric cases where surface elec-
niques [40, 25]. The examples that follow are trodes may be used effectively to assess rod
discussed in relation to common presenting photoreceptor activity (see below). Photopic
symptoms. Such a classification inevitably re- cone-mediated ERGs are less severely affected
sults in a degree of overlap; selected examples than rod-driven ERGs in RP, but usually show
are used here to illustrate this integrated delayed implicit time and amplitude reduction,
approach to visual electrodiagnosis. best seen in the 30-Hz flicker response. The de-
gree of central retinal involvement in RP can be
indicated by the PERG; some patients with RP
9.3 and preserved central vision have an almost un-
Investigation of Night Blindness detectable full-field ERG but a normal PERG
P50 component (Fig. 9.3) consistent with macu-
Correct early diagnosis of night blindness is lar sparing [40, 72, 73]. However, the PERG P50
important because it may be the presenting component can be abnormal in the presence of
symptom of a progressive retinal dystrophy normal visual acuity [40, 72, 73] and may have
with significant implications for vision. How- some prognostic value in predicting involve-
ever, it may reflect a stationary disorder such ment of central vision. Although difficult for
as congenital stationary night blindness young children to perform, multifocal ERG may
(CSNB); electrophysiology enables the distinc- play a similar role to PERG in the assessment of
tion. Symptoms of night blindness are not al- macular function.
ways obvious, particularly in infants and young In X-linked RP, accounting for about 5–20 %
children. of all familial cases [35], the ERG is usually un-
detectable or grossly subnormal from an early
age (Fig. 9.3 D). Asymptomatic female hetero-
9.3.1 zygotes may show a prominent tapetal reflex
Retinitis Pigmentosa and there may be intraretinal bone-spicule pig-
(Rod–Cone Dystrophy) mentation, although the fundus can be normal.
The incidence of ERG abnormality in X-linked
Retinitis pigmentosa (RP) is a heterogeneous carriers is high and may involve amplitude or
group of disorders characterised by progressive implicit time [3, 9] in both rod and/or cone
dysfunction affecting the rod more than the ERGs. The ERG findings in heterozygotes may
cone photoreceptors (a rod–cone dystrophy). show significant interocular asymmetry, unlike
138 Chapter 9 Paediatric Electrophysiology: A Practical Approach

Fig. 9.2. Pattern and flash ERGs in a normal subject apart from the PERG in patient D, which was obtained
(N), in a 2-year-old patient with complete CSNB (A), using gold foil corneal electrodes. Comparison of A
in a 6-year-old patient with Leber congenital amauro- with Fig. 9.4A and C with Fig. 9.5C demonstrates the
sis (B), in a 1-year-old monochromat (C) and in a 7- qualitative similarity of surface and corneal record-
year old patient with X-linked retinoschisis (D). All ings. See text for details
recordings were taken with surface eyelid electrodes
 9.3 Investigation of Night Blindness 139

Fig. 9.3. Typical findings in a normal subject (N) and and normal visual acuity (6/9). In patient B (aged
in four patients with rod–cone dystrophy. Maximum 11 years), PERG P50 component and visual acuity are
ERG a-waves are reduced, consistent with rod pho- mildly reduced (6/12). In C (aged 10 years) PERG 50 is
toreceptor dysfunction. Photopic ERGs are reduced severely reduced, consistent with severe macular in-
and delayed, indicating significant but less severe cone volvement and significant visual acuity impairment
system dysfunction. Pattern ERGs in patient A (aged (6/60). The ERG findings in patient D (aged 7 years),
9 years) are normal, in keeping with macular sparing with X-linked disease, are typically severe
140 Chapter 9 Paediatric Electrophysiology: A Practical Approach

most hemizygotes. ADRP is more often associ- (Figs. 9.4A, 9.2A) has an undetectable rod-spe-
ated with a milder clinical course and less severe cific ERG. The cone flicker and photopic (single
ERG changes in affected children. Autosomal flash) ERGs show distinctive abnormalities. The
recessive RP is very heterogeneous and both photopic ERG has a broad a-wave followed by a
severe and mild variants are seen. b-wave lacking photopic oscillatory potentials
RP of varying severity is associated with syn- and showing a low b:a ratio. This appearance is
dromic disorders such as Bardet-Biedl (BBS) thought to reflect loss of cone ON-bipolar con-
and Usher syndromes, although a cone–rod tribution but preservation of the OFF- pathway
pattern of dysfunction can occur in BBS [35]. found in long and medium wavelength cone
Full-field ERGs in Usher syndrome are typically systems [40]. This is confirmed by the results of
markedly abnormal [24]. long duration ON- OFF- ERGs [65], which reveal
a normal a-wave, a selectively diminished ON-
b-wave and preservation of the OFF- d-wave,
9.3.2 consistent with involvement of the depolarising
Congenital Stationary Night Blindness ON-bipolar cell pathway. S-cone ERGs are also
affected, confirming the defect to be post-pho-
Most forms of CSNB manifest an ERG maximal totransduction in rods and all cone types
response with a normal a-wave and selective (Fig. 9.4A). The electroretinographic changes in
b-wave reduction, a negative or electronegative cCSNB are identical to those in melanoma-asso-
ERG, consistent with abnormalities that are ciated retinopathy [40, 46] and although un-
post-phototransduction. It is usually best seen in likely to be of relevance in paediatric practice,
the scotopic rod-dominated maximal ERG, al- demonstrate the importance of always placing
though it may also occur in cone-mediated ERGs electrophysiological data in clinical context.
under photopic conditions [46, 65]. Rare forms of Although also showing a profoundly elec-
CSNB manifest ERG maximal response a-wave tronegative maximal ERG, iCSNB typically has a
reduction consistent with disruption of rod pho- detectable, but subnormal or delayed, rod-spe-
toreceptor dysfunction and are reviewed else- cific ERG. These are accompanied by a subnor-
where [23]. CSNB is genetically heterogeneous mal, delayed 30-Hz flicker ERG that has a typi-
with AD, AR and X-L inheritance reported. cally bifid appearance (Fig. 9.4 B). The photopic
X-linked CSNB usually presents with nystag- single flash ERG may be markedly subnormal
mus and poor vision in infancy. The night and occasionally has an electronegative wave-
blindness usually only becomes apparent at an form [85]. Overall, the cone-mediated photopic
older age. Most children are myopic and strabis- ERG abnormalities in iCSNB are more apparent
mus is common. X-linked CSNB can be sub- than those of cCSNB (Fig. 9.4 B); both ON- and
divided into complete (cCSNB) and incomplete OFF- responses are affected [65].
(iCSNB) forms, a division originally based on Dominant forms of CSNB may also be asso-
electrophysiology and psychophysics [64] and ciated with an electronegative ERG resulting
now known to reflect genetically distinct disor-
ders. The gene for cCSNB maps to Xp11.4, and
results from mutation in NYX which encodes
nyctalopin, believed to play a role in the devel-
opment of retinal interconnections involving Fig. 9.4. Pattern ERGs, full-field ERGs, including
the ON-bipolar cells [6]. The gene for iCSNB ON-OFF- and S-cone ERGs in a normal subject (N)
(CACNA1F) maps to Xp11.23 and encodes a and in patients with complete CSNB (A), incomplete
pore-forming subunit of an L-type voltage-gat- CSNB (B) and enhanced S-cone syndrome (C). In the
ed calcium channel believed to modulate gluta- latter case, note the S-cone-specific recordings are
similar to those of the single flash photopic ERG. See
mate release from photoreceptor presynaptic text for details. Eye movement or blink artefacts, com-
terminals [5]. monly present in paediatric ERGs to bright flashes,
Both X-linked forms of CSNB have markedly occur at about 100 ms, most prominently in the max-
electronegative maximal ERGs. The cCSNB imal ERG of patient B
9.3 Investigation of Night Blindness 141
142 Chapter 9 Paediatric Electrophysiology: A Practical Approach

from post-phototransduction rod system in- and may have relatively mild visual field loss.
volvement. Some authors report sparing of the The fundus appearance is characterised in old-
cone system [69], but others, using additional er children and adults by nummular pigment
short wavelength stimulation, identified in- deposition around the arcades at the level of the
volvement of the S-cone system [45]. The PERG RPE. They may eventually develop degenerative
is normal in such cases. In some dominant changes in the region of the vascular arcades. In
forms of CSNB, there is ERG maximal response young children, the fundus changes are very
a-wave reduction consistent with disruption of subtle or nonexistent and the ERG is key to
phototransduction or rod photoreceptor func- making the correct diagnosis.
tion (see [23] for a recent review). Patients with The ERGs in ESCS are pathognomonic for the
recessive CSNB and an electronegative maximal disorder (Fig. 9.4 C). Full-field ERGs show mini-
ERG can have other ERG features that may re- mal differences in waveform between photopic
semble either the complete or incomplete forms and scotopic ERGs elicited by the same intensity
of X-linked disease (unpublished data). stimuli. Flicker ERGs are markedly delayed and
Fundus albipunctatus is a recessively inherit- subnormal and are distinctive in that the flicker
ed, probably stationary disorder of night vision ERG amplitude, which normally lies between
associated with a mutation in RDH5 encoding that of the photopic a- and b-waves, is of lower
the RPE enzyme retinol dehydrogenase [23]. amplitude than the photopic a-wave. In ESCS,
The clinical symptoms relate to impaired regen- there is increased sensitivity to short wavelength
eration of rhodopsin. Funduscopy reveals mul- stimulation. ON-OFF ERGs to longer wave-
tiple yellow-white dots located at the level of the lengths, mediated predominantly by L and M
RPE in the mid-periphery. The ISCEV standard cones, show marked reduction (Fig. 9.4 C). Pat-
ERG in such patients shows an undetectable tern ERG reduction may occur and the P50 com-
rod-specific ERG and a mildly reduced ampli- ponent may be markedly delayed.
tude a-wave with a lower amplitude b-wave
[66]. However, with sufficiently long dark adap- Summary for the Clinician
tation, usually 2 h or more, rod-derived ERGs RP
become normal. A normal or significantly im- ∑ Patients with RP typically present with
proved ERG following extended dark adapta- progressive night blindness and visual field
tion enables fundus albipunctatus to be distin- constriction
guished from retinitis punctata albescens, a ∑ Classical signs include bone-spicule
progressive retinal degeneration that also pres- pigmentation, vessel attenuation and disc
ents with a flecked retinal appearance accompa- pallor, but the fundus may be normal
nied by markedly abnormal ERGs that do not ∑ Bright flash scotopic ERGs show a reduced
normalise following prolonged dark adapta- a-wave, indicating rod photoreceptor
tion. dysfunction with less severe photopic ERG
abnormalities
∑ Pattern ERGs can be used to assess the
9.3.3 degree of macular involvement
Enhanced S-Cone Syndrome
CSNB
Enhanced S-cone syndrome (ESCS) is an auto- ∑ Patients typically present with nonprogres-
somal recessive trait consequent upon mutation sive night blindness
in NR2E3 [30].A single histological report, in an ∑ X-linked CSNB is characterised by an
advanced case, showed an absence of rods and electronegative maximal scotopic ERG,
increased numbers of cones, 92 % of which were indicating dysfunction that is post-photo-
thought to be S-cones, with 15 % expressing the transduction.
L/M cone opsin including some which co-ex- ∑ Electroretinography enables the distinction
pressed S-cone opsin [63]. Patients typically between complete and incomplete X-linked
present with night blindness or maculopathy and other less common forms (see above)
 9.4 Early Onset Nystagmus 143

ESCS small percentage of patients with bull’s eye

∑ ESCS is a rare recessively inherited disorder maculopathy to have cone dystrophy [50]. Visu-
characterised by an absence of rods and an al fields typically reveal central scotomata,
abnormally high number of cones sensitive although peripheral field loss, depressed sensi-
to short wavelength stimulation tivity and ring scotomata may occur. Inheri-
∑ Patients typically present with night tance may be autosomal recessive, dominant or
blindness or maculopathy X-linked (see Ret Net for genetic subtypes).
∑ ERGs are pathognomonic for the disorder Strictly, the ERG abnormalities in cone
(see above) dystrophy are confined to the cone system
(Fig. 9.5 A), but mild additional rod involve-
ment may occur in some patients late in the
9.4 disease. Both cone and rod ERG abnormalities
Early Onset Nystagmus occur in cone–rod dystrophy, with the cone
responses being more affected (Fig. 9.5 B).
Early onset nystagmus is seen in three main Usually, the 30-Hz flicker response is subnor-
clinical situations. Firstly, in children with neu- mal and of increased implicit time. For example,
rological disorders; secondly in children with the dominant cone–rod dystrophy associated
afferent visual failure; and finally in congenital with mutation in GUCY2D, (encoding retinal
idiopathic motor nystagmus (CIMN). The main guanylate cyclase) is associated with both with
diagnostic dilemma is in differentiating CIMN 30-Hz flicker delay and amplitude reduction
from sensory forms of nystagmus in a child with milder rod-system dysfunction [22]. Clini-
with nystagmus and a normal fundus [29]. Sen- cally, these patients have poor vision in bright
sory nystagmus may be associated with a num- light from childhood, but major reduction in vi-
ber of disorders including CSNB (Sect. 9.3.2), sual acuity occurs after the late teens. Fundus
retinal dystrophies, cone-system dysfunction abnormalities are confined to the central macu-
syndromes, albinism and optic nerve abnor- la, and the central atrophy increases with age.
malities. Full-field ERGs can identify a retinal PERGs are usually markedly reduced or unde-
aetiology and, when combined with VEP tectable.
recordings, may localise dysfunction to the lev- The macular changes in some patients with
el of the retina or optic pathways or exclude a cone dystrophy may be absent or subtle, and as-
sensory cause. Equally, exclusion of afferent vi- sociated disc pallor may mistakenly be thought
sual pathway dysfunction may be an important to reflect primary optic nerve disease [68, 74].
contribution to management. Pattern VEP delay is common in macular dys-
function [40], and a delayed VEP should not be
interpreted as reflecting optic nerve dysfunc-
9.4.1 tion without a measure of the retinal response
Cone and Cone–Rod Dystrophy to a similar stimulus. The pattern ERG P50 com-
ponent is subnormal in macular dysfunction: in
Patients with cone or cone–rod dystrophy typi- mild disease there is P50 reduction with con-
cally present with progressive impairment of comitant reduction in N95; in severe disease the
central vision, abnormalities of colour vision, PERG is extinguished. These findings are con-
photophobia and often nystagmus [78], although trasted with those in optic nerve/retinal gan-
there are exceptions [21]. There is wide pheno- glion cell disease where P50 is usually intact,
typic variability and although the fundus may and the abnormality is confined to the N95
initially appear normal, abnormalities can in- component (see below). The differential effect
clude peripheral hypopigmentation and/or pig- of ganglion cell dysfunction and macular dis-
ment clumping, disc pallor, macular atrophic ease on the PERG facilitates accurate interpreta-
changes or bull’s eye maculopathy. Interestingly, tion of a delayed PVEP in the patient with visu-
a recent prospective study identified only a al symptoms.
144 Chapter 9 Paediatric Electrophysiology: A Practical Approach
 9.4 Early Onset Nystagmus 145

S-cone monochromatism is usually an X-

Fig. 9.5. Pattern ERGs and full-field ERGs in a nor-
mal subject (N) and in patients with cone dystrophy linked disorder in which there is absent L- and
(A), cone–rod dystrophy (B), S-cone monochroma- M- cone function. The presentation in infancy is
tism (C), Stargardt fundus flavimaculatus group 1 (D) similar to rod monochromatism but the visual
and juvenile onset Batten disease consequent upon acuity is better (typically between 6/24 and
CLN3 (E). Prominent blink artefacts occur in maxi- 6/60) and the refractive error is usually myopic.
mum ERG waveforms in A, B, C and D at about 100 ms Spectral sensitivity measurement can distin-
and have been omitted from E for clarity. Patient C
guish S-cone monochromatism from rod mono-
had a preserved S-cone ERG (not shown). See text for
details chromatism, as can specialised colour vision
testing [10], but these tests are not possible in
infancy. ERG abnormalities are similar to those
observed in the rod monochromat (Fig. 9.5 C)
except that the S-cone-specific ERG, a response
9.4.2 to a short-wavelength stimulus recorded in the
Leber Congenital Amaurosis presence of longer wavelength adaptation, is
preserved. A similar electrophysiological phe-
Leber congenital amaurosis (LCA) accounts notype may be seen in achromatopsia associat-
for approximately 15 % of congenital blindness. ed with recessively inherited mutation in
This largely recessively inherited disorder man- GNAT2 [61].
ifests with signs of very poor visual function
and roving eye movements or nystagmus. Eye-
poking or eye-rubbing, the oculodigital sign, 9.4.4
may be present and may eventually lead to Albinism
sunken orbits, cataract and keratoconus. The
majority of patients have normal fundi at pres- Albinism describes a group of inherited condi-
entation, but disc pallor, vessel attenuation and tions characterised by disorders of melanin
pigmentary changes may follow. The ERG is synthesis affecting the eyes (ocular albinism)
typically severely reduced or undetectable from or the eyes, skin and hair (oculocutaneous al-
early infancy (Fig. 9.2 B). binism). Children with albinism usually present
with nystagmus and poor visual acuity in early
infancy. Classical signs include iris transillumi-
9.4.3 nation, fundus hypopigmentation and foveal
Cone Dysfunction Syndromes hypoplasia. There is a high incidence of strabis-
mus and significant refractive error. In both
Rod monochromatism is an autosomal reces- oculocutaneous and ocular albinism, there is an
sive disorder characterised by poor vision from abnormally high percentage of decussating
birth, nystagmus and photophobia and is temporal optic nerve fibres from each eye that
consequent upon mutations in CNGA3 or project to the contralateral hemisphere. This
CNGB3 [62]. Patients usually attain acuities intracranial misrouting is demonstrated by the
of about 6/60 and have absent colour vision. presence of contralateral VEP predominance
Most patients are hyperopic. The fundus is (Fig. 9.6), being of higher amplitude and/or
usually normal, although some granularity shorter latency over the contralateral hemi-
of the central macula may develop with time. sphere [20, 67]. Flash VEPs are most sensitive to
The ERG reveals an absent or severely reduced misrouting in infants and young children and
30-Hz flicker response, but good rod ERGs pattern onset-offset VEPs are most sensitive in
following even a limited period of dark adap- adolescents; between the ages of 5 and 14 years,
tation (Fig. 9.2 C). Minor reduction in ma- the use of both techniques optimises sensitivity
ximum ERG a-wave may reflect the absence of [67]. Pattern reversal stimulation is not appro-
the cone contribution from this mixed re- priate; firstly, most patients have nystagmus and
sponse. secondly, reversal VEPs are subject to the phe-
146 Chapter 9 Paediatric Electrophysiology: A Practical Approach

Fig. 9.6. Monocular flash VEPs in a 1-year-old pa- tude over the contralateral compared with the ipsilat-
tient recorded using five posteriorly situated elec- eral hemisphere, in keeping with the optic nerve mis-
trodes; each referred to a mid frontal reference (Fz). routing associated with albinism
Flash VEPs are of shorter latency and higher ampli-

nomenon of paradoxical lateralisation [4]. Both

of these factors confound accurate interpreta- Summary for the Clinician
tion of pattern reversal VEPs but do not apply to Cone or cone–rod dystrophy
VEPs elicited using brief pattern onset stimula- ∑ Patients with cone or cone–rod dystrophy
tion. typically present with progressive loss in
visual acuity, abnormal colour vision,
photophobia and often nystagmus
9.4.5 ∑ The fundus may initially appear normal,
Optic Nerve Hypoplasia but abnormalities can include peripheral
hypopigmentation and/or pigment clump-
Infants with severe bilateral optic nerve hypo- ing, disc pallor, bull’s eye maculopathy or
plasia (ONH) usually present with nystagmus macular atrophy
and poor vision. Although these patients have ∑ Cone system photopic ERG’s are reduced
small pale optic discs, the optic nerve abnormal- and usually delayed in cone dystrophy with
ity may easily be missed when examining a small additional involvement of rod-dominated
infant with nystagmus. Electrophysiological scotopic ERGs in cone–rod dystrophy
testing is extremely useful in detecting visual ∑ Pattern ERGs are usually markedly reduced
pathway abnormalities and may prompt review or undetectable
of the optic disc appearance. It is important to
make a specific diagnosis, as ONH may be asso- Leber congenital amaurosis
ciated with endocrine abnormalities, particular- ∑ Severe visual impairment and roving
ly growth hormone deficiency, which need treat- eye movements or nystagmus from birth
ment. Pattern and Flash VEPs show varying or early infancy
degrees of attenuation and delay [2, 49] and may ∑ Fundi are typically normal at presentation,
be undetectable in severe cases. ERGs are nor- but disc pallor, vessel attenuation and
mal and may be of high amplitude [13, 48]. pigmentary changes may follow
 9.6 Investigation of Children Who Present with Unexplained Visual Acuity Loss 147

∑ The ERG is severely reduced or unde- Peroxisomal disorders result from dysfunc-
tectable from early infancy, indicating tion or absence of peroxisomes and may be asso-
severe photoreceptor dysfunction ciated with pigmentary retinopathy resulting in
severe ERG abnormalities [36]. Zellweger syn-
Rod or S-cone monochromatism drome is characterised by infantile retinal degen-
∑ Poor vision, nystagmus, photophobia and eration that is associated with facial dysmorphia,
abnormal colour vision from birth hypotonia,psychomotor retardation,seizures,re-
∑ Fundi are usually normal but maculae may nal and hepatic abnormalities. Patients with
appear granular neonatal adrenal leukodystrophy may present in
∑ Full-field ERGs reveal an absent or severely infancy, but they generally survive until age
reduced photopic 30 Hz flicker response, 7–10 years. Flash ERGs have been documented as
but good rod ERGs following even a limited undetectable [27]. Less severe findings are pres-
period of dark adaptation ent in infantile Refsum disease, so-called because
of elevated serum phytanic acid.
Albinism Cortical visual impairment (CVI) is a condi-
∑ Classical signs include foveal hypoplasia, tion resulting in bilateral visual impairment
iris transillumination and fundal hypopig- caused by nonocular damage to the visual path-
mentation in addition to nystagmus ways or cortex. The most common cause of CVI
∑ VEPs are of higher amplitude and/or shorter is hypoxic birth injury, although other causes
latency over the contralateral hemisphere in include trauma, shunt failure leading to occipi-
keeping with an abnormally high percentage tal lobe infarction, meningitis, encephalitis,
of decussating temporal fibres from each eye congenital toxoplasmosis, neonatal herpes sim-
that project to the contralateral hemisphere plex, cardiac failure and infantile spasms. Flash
ERGs may be useful in excluding a retinal cause
of visual failure. Flash visual evoked potentials
9.5 may confirm CVI and may be of prognostic
Visual Impairment value [17].
in Multisystem Disorders

The neuronal ceroid lipofuscinoses (NCLs) are a 9.6

group of recessively inherited neurodegenerative Investigation of Children Who Present
storage disorders associated with progressive with Unexplained Visual Acuity Loss
neurological failure and retinal degeneration.
The juvenile onset form (Batten disease), relating Visual loss in childhood may be due to macular
to mutation in CLN3, is of particular interest as disease, optic neuropathy or nonorganic visual
patients often present with visual acuity reduc- loss, and electrophysiology not only allows
tion prior to the development of neurological these to be distinguished but may also indicate
symptoms. At this stage, there may be a bull’s eye a specific diagnosis.
maculopathy or the fundus may be normal.In the
latter case, nonorganic visual loss may be sus-
pected.Abnormal pattern ERGs indicate macular 9.6.1
dysfunction [58]. The maximal ERG response is Macular Dystrophies
electronegative, but some patients will also show
some a-wave reduction consistent with loss of Inherited macular dysfunction can occur either
photoreceptor outer segments [55, 84]. Photopic in association with generalised retinal dysfunc-
ERGs may also show a markedly reduced b:a ra- tion or as disturbance of function confined to
tio, a relatively unusual finding that may serve to the macula (a macular dystrophy). Full-field
alert to the diagnosis (Fig. 9.5E); the flicker ERG ERG allows assessment of generalised retinal
is profoundly delayed. With time, the ERG be- function and the pattern ERG P50 component
comes undetectable. allows assessment of macular function.
148 Chapter 9 Paediatric Electrophysiology: A Practical Approach

9.6.1.1 Full-field ERGs are normal but the electro-ocu-

Stargardt Macular Dystrophy–Fundus logram (EOG) light rise is severely reduced or
Flavimaculatus undetectable, in keeping with severe gener-
alised dysfunction affecting the RPE–photore-
Stargardt macular dystrophy–fundus flavimac- ceptor interface. The EOG is abnormal during
ulatus (S-FFM) is an autosomal recessive disor- the asymptomatic previtelliform stage. Pattern
der consequent upon mutation in ABCA4 [1]. ERGs are typically normal until the vitellirup-
Patients often present in adolescence with pro- tive stage, when there is visual acuity loss and, at
gressive visual acuity reduction. On examina- that stage, PERG reduction. Patients younger
tion, there is usually macular atrophy and asso- than about 6 years are unlikely to be able to
ciated white flecks at the level of the retinal comply with EOG testing, but as the disorder is
pigment epithelium. In children with S-FFM, dominantly inherited it is appropriate to test the
there may be significant visual loss before there parents.
is significant fundus change, and it is in these
cases where electrophysiological testing is most 9.6.1.3
useful. Most patients with S-FFM have severe X-Linked Juvenile Retinoschisis
macular dysfunction and show severe PERG
P50 reduction, even though visual acuity may be Although, strictly, full-field ERG abnormalities
relatively well preserved. In some patients, dys- imply generalised retinal dysfunction, X-linked
function is confined to the macula (group 1) but retinoschisis (XLRS) may be referred to as a
in others there may be generalised involvement macular dystrophy. Patients typically present in
of the cone system (group 2) or rod and cone the 1st or 2nd decade with reduced visual acuity,
systems (group 3). The presence of a normal and macular abnormalities are present in most
ERG at any stage during the course of the disor- cases. Classically, these have a “spoke wheel”
der appears to be associated with a good prog- appearance due to the presence of foveal micro-
nosis for retention of peripheral retinal func- cysts. The retinal cleavage may be revealed by
tion [53, 54]. Despite inter-sibling variation in optical coherence tomography [80]. With time,
clinical phenotypic features, such as fundus ap- these radial cystic changes may give way to non-
pearance and visual acuity, the electrophysio- specific macular atrophy. Peripheral schisis le-
logical grouping is concordant across sibling sions are only present in 50 % of patients, most-
pairs [53], unlike patients with bulls’ eye macu- ly in the infero-temporal quadrant. In older
lopathy [50, 43]. Typical findings in a young patients with nonspecific macular atrophy, but
patient with S-FFM (group 1) are shown in no peripheral schisis, the diagnosis may not be
Fig. 9.5D. obvious and electrophysiology may be instru-
mental in making the diagnosis or suggesting a
9.6.1.2 candidate gene. An electronegative maximal
Best Vitelliform Macular Dystrophy ERG is typically present (Fig. 9.2 D), although
the degree of abnormality can vary and in rare
Best vitelliform macular dystrophy is an auto- cases b-wave amplitudes have been reported as
somal dominant disorder caused by mutations normal [11]. Rod-specific ERGs are usually
in VMD2, which encodes bestrophin [70]. Best undetectable or markedly reduced in keeping
disease usually has a childhood or teenage onset with the intraretinal cleavage [80] and typical
and in the early stages is typically characterised maximal response ERG b-wave abnormality.
by a well-circumscribed vitelliform macular le- Photopic and 30-Hz flicker ERGs are usually
sion, resulting from accumulation of lipofuscin subnormal and delayed. The ON- b-wave may
at the level of the RPE. Visual acuity is usually be reduced with preservation of the OFF-
normal until the subsequent vitelliruptive stage, d-wave in some patients [89], but in others the
resulting in disruption of overlying photorecep- OFF- d-wave may also be affected. Pattern ERGs
tors and eventual macular atrophy. The electro- are usually markedly reduced in keeping with
physiology in Best disease is characteristic. macular dysfunction [18, 80]. The presence of
 9.6 Investigation of Children Who Present with Unexplained Visual Acuity Loss 149

an electronegative ERG in a patient with a mac- features include centrocaecal scotoma, dyschro-
ular lesion, even if atypical, may suggest XLRS1 matopsia, pallor of the optic disc and loss of the
as a suitable candidate gene for analysis. Severe papillomacular bundle [16, 82]. Histopathologi-
cases of XLRS may also have an abnormal cal studies suggest that the fundamental pathol-
a-wave reflecting some photoreceptor loss, ogy is degeneration of the retinal ganglion cells
possibly consequent upon haemorrhage or full- [44]. The PERG shows N95 loss that can occur
thickness detachment early in life. before a VEP abnormality. The PVEP is often
markedly delayed and can vary in amplitude
Summary for the Clinician from subnormal to undetectable in end-stage
Stargardt–fundus flavimaculatus (S-FFM) disease. In severe long-standing disease, signifi-
∑ Fleck lesions in the posterior pole extend- cant PERG P50 component amplitude reduction
ing to the mid-periphery, usually with may occur, often accompanied by a shortening
central atrophy of implicit time, in keeping with the loss of gan-
∑ PERG usually undetectable – severe glion cell contribution to both the N95 and P50
macular dysfunction components [42, 81]. Typical findings are shown
∑ Some patients have generalised ERG abnor- in Fig. 9.7.
malities that may be of prognostic value Most patients with Leber hereditary optic
neuropathy (LHON) present with acute painless
Best disease sequential bilateral disc swelling and visual loss
∑ Typically characterised in the early stages between 11 and 30 years of age, but there are
by a well-circumscribed vitelliform macu- reports of much earlier and much later age of
lar lesion onset [8, 41]. There are few reports of the PERG
∑ Characterised by normal full-field ERGs in LHON, but N95 reduction may occur [8, 39].
but an absent or severely reduced EOG light This is accompanied by a normal PERG P50
rise component and normal full-field ERGs. One
∑ Pattern ERGs are typically normal until the case report [59] describes recordings taken
vitelliruptive stage, when there is visual 3 days after the acute onset of visual loss in the
acuity loss and PERG reduction second eye of a young male patient (11778 muta-
tion). There had been sudden reduction in
X-linked retinoschisis vision in the first eye 3 weeks earlier. Both eyes
∑ Classically, a “spoke wheel” appearance at showed prominent N95 reduction in the PERG,
the fovea that is replaced by nonspecific but P50 was normal and there was no interocu-
macular atrophy with age lar asymmetry. The N95 loss in the more recent-
∑ Electronegative ERG appearance indicating ly affected eye was attributed to primary
dysfunction post-phototransduction or ganglion cell dysfunction; more time would be
inner retinal required for retrograde degeneration to have
∑ Pattern ERGs are usually markedly reduced occurred.

9.6.2.2
9.6.2 Compressive Lesions
Optic Nerve Dysfunction
Optic nerve glioma in children may be associat-
9.6.2.1 ed with painless visual loss, proptosis or squint,
Familial Optic Atrophy although patients are often asymptomatic,
especially when associated with neurofibro-
The commonest cause of familial optic nerve matosis. Optic disc swelling and atrophy
dysfunction is dominant optic atrophy (DOA), may occur. There may be chiasmal involvement
related to mutation in OPA1. Patients typically and presentation will depend upon the location
present with painless, progressive visual acuity of the tumour and the age of the patient. Pattern
loss that may be asymmetrical. Other clinical VEPs often show marked attenuation, broaden-
150 Chapter 9 Paediatric Electrophysiology: A Practical Approach

Fig. 9.7. Pattern and flash VEPs

and pattern ERGs from a
normal subject (N) and from
right and left eyes of a 9-year-
old patient with dominant
optic atrophy. Pattern VEPs
are abnormal, PERG N95:P50
amplitude ratio is reduced
and P50 is of shortened implicit
time, consistent with ganglion
cell disease (see text for details)

ing and delay. Flash VEPs may be less severely in the misrouting of albinism. Stimulus param-
affected. With chiasmal involvement, the eters are of crucial importance to accurate
occipital distribution of VEPs from the fellow localisation. In general, use of a large field,
eye may additionally demonstrate a degree large check stimulus gives paradoxical laterali-
of interhemispheric asymmetry. sation [4, 34], whereas a small field, small check
The signs and symptoms in craniopharyn- stimulus gives anatomical lateralisation. Un-
gioma vary greatly depending on the neural crossed asymmetries have also been reported
structures affected but commonly involve to reflect unilateral post-chiasmal compression
headache, vomiting and visual disturbance [49].
[19]. Nystagmus has been reported in some
cases. Anterior extension to the optic chiasm Summary for the Clinician
can result in bitemporal hemianopia, unilateral Familial optic atrophy
temporal hemianopia, papilledema, or uni- ∑ The PERG shows N95 loss that can occur
lateral/bilateral decrease in visual acuity. before a VEP abnormality in DOA. PERG
Children are often inattentive to visual loss P50 component amplitude reduction may
and formal testing may be required. Monocular occur in severe long-standing disease sig-
pattern VEPs frequently reveal a crossed asym- nificant, usually accompanied by a shorten-
metry where there is an abnormal distribution ing of implicit time
over the two hemispheres which reverses ∑ The PVEP may be markedly delayed and
on monocular stimulation of the other eye can vary in amplitude from subnormal to
and which is opposite in nature to that seen undetectable in end-stage disease
 9.7 Unexplained Visual Loss in the Normal Child 151

9.7 9.7.2
Unexplained Visual Loss Nonorganic Visual Loss
in the Normal Child
The VEP, combined with other electrophysiolog-
In most children that present with acquired ical tests, is crucial to the diagnosis of nonorgan-
visual loss, the cause of the impairment is re- ic visual loss. Electrophysiological testing may
vealed by careful ophthalmological examina- demonstrate normal function in the presence of
tion. However, some children with retinal dys- symptoms that suggest otherwise or may quanti-
trophies may have a normal fundus or very fy the level of genuine dysfunction in the pres-
subtle changes in the early stages and electro- ence of functional overlay. Flash VEPs in nonor-
physiological testing is fundamental to making ganic visual loss are normal [33, 51]. A well-
the correct diagnosis. Equally, there is a higher formed pattern reversal VEP is incompatible
incidence of nonorganic visual loss in a paedi- with a visual acuity of approximately 6/36 or
atric population.Any acuity reduction in a child worse [32]. The pattern onset or appearance VEP
should probably be regarded as organic until (PaVEP) is more susceptible to blur than the pat-
proven otherwise. The objective data provided tern reversal VEP and it is the authors’experience
by electrophysiology is extremely helpful in the that the PaVEP enables a more direct relation-
diagnosis of nonorganic visual loss. ship to be established between visual acuity and
Children with high ametropia have a signifi- the presence or absence of a response to small
cantly higher rate of retinal electrophysiological check sizes of varying contrast. Constant encour-
abnormalities compared with lower refractive agement and direct monitoring of fixation and
errors or emmetropia [26]. Electrophysiological compliance are essential in all patients suspected
testing, to rule out associated retinal pathology, of hysteria or malingering and will often result in
should be considered in cases of high ametropia improved patient cooperation. Careful observa-
in childhood when correction of the refractive tion of the background electroencephalographic
error does not result in normal acuity. (EEG) input and the developing averaged VEP is
advisable; children may find the alternating
checkerboard hypnotic and the appearance of an
9.7.1 alpha rhythm in the ongoing EEG may indicate
Amblyopia drowsiness or loss of concentration. Equally, a
tendency for the P100 component to broaden or
Children suspected of being amblyopic are gen- increase in latency in the acquired average sug-
erally referred for electrodiagnostic testing in gests that accommodation or fixation is unsatis-
order to exclude other pathologies, e.g., when factory. It may be necessary to stop averaging
visual acuity has not improved with patching after fewer sweeps than usual to prevent wave-
and the fundi are normal or when visual acuity form deterioration. Simultaneous PERG record-
is reduced bilaterally. In amblyopic eyes, pattern ing may be beneficial. The PERG P50 component
visual evoked potentials often show amplitude is very susceptible to deterioration with poor
reduction and/or mild to moderate delay [75, compliance, and a normal PERG can only be ob-
79] that is not due to optical factors [52]. Gener- tained with satisfactory fixation and accommo-
ally, latency abnormalities in the major positive dation. Routine ERG should also be performed;
(P100) component tend to be milder in ani- ERGs can be markedly abnormal in retinal dys-
sometropic than with strabismic amblyopia. function with no or minimal fundus abnormali-
Pattern VEPs may also play a useful role in mon- ty but constricted visual fields,and field loss is of-
itoring the effects of patching therapy in ambly- ten a feature of nonorganic visual loss. PERG and
opic and fellow eyes [83, 87]. PVEP findings may be normal in such conditions
if the maculae are spared.
Normal electrophysiology does not preclude
the presence of some underlying organic dis-
152 Chapter 9 Paediatric Electrophysiology: A Practical Approach

ease [31, 38], but the demonstration of normal

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