Normal Postnatal Ocular Development

1
Laura J. Heinmiller and Alex V. Levin

Although detailed normative data regarding the volumetric old infants had a preference for a face-like stimulus over a
and topographical analysis of the eyeball and its contents are scrambled face image. Both of these were preferred by the
available [1] this discussion will be confined to the clinically infant over a blank face image [4]. One and four month old
relevant dimensions. infants show greater pupillary dilation (a substitute measure
for arousal and interest) to faces than to other nonsocial pat-
terns [5]. By 12 weeks of age only 5 % will not fixate on a
Visual Acuity light although 13 % do not fixate well [6]. Actually, by
12 weeks, half appear to fixate clinically but do not accom-
Fixation modate to focus as judged by the appropriate change in the
red reflex [6]. By 6 months, almost 100 % will both fixate
Perhaps the most frequent question which parents ask per- and focus normally with either eye although some research-
taining to their infant’s eyes is “What does my baby see?” The ers believe that full adult fixational behavior is not achieved
answer to this question depends in part on the type of method until 1 year [6]. Both eyes do not have to develop normal
used to assess visual acuity. The majority of babies should fixational behavior symmetrically [6]. By 6 months, only 4 %
show some fixational behavior at term birth. At 4 weeks, the of children will have be a fixational abnormality in one eye
baby looks at their mother’s face while breast feeding [2]. due to an underlying ocular problem [6].
When the mother moves her face, the child will follow it visu-
ally. This movement is interrupted if the mother turns her face
away so that only her profile is presented [2]. By 2 months the Optokinetic Nystagmus (OKN)
baby is following better but the pursuit movements tend to be
jerky rather than smooth [2]. Smooth pursuit eye movements More objective values for visual acuity in infants depend
show the most maturation from 2 to 6 months old, and reach- largely on the method used. In a comparative review of the
ing almost an adult-like gain by 18 months old [3]. Pieh and literature, Dobson and Teller found that visual acuity in the
coworkers found that tracking time was highest when a larger first month of life measured 20/200–300 by observation of
stimulus of 4.78° of visual angle was applied (p < 0.022) and optokinetic nystagmus (OKN), visual evoked potentials
when the stimulus was moved at a medium stimulus velocity (VEP) or preferential looking responses [7]. By 6 months the
of 15 degree/s (p < 0.0002) [3]. vision improved to 20/100–200 by OKN and preferential
Often, the human face is a better stimulus of fixation than looking but to 20/25 by VEP [7]. Normal values for grating
a light source [2]. Goren et al. were able to show that 9 min acuity and OKN have been developed for the first 3 years of
life [8]. The range of normal values is very wide in the first
6 months. Visual development, as measured by these tools,
L.J. Heinmiller, M.D. appears to accelerate in the second year of life [8].
Pediatric Ophthalmology and Ocular Genetics, Wills Eye Hospital,
840 Walnut Street, Ste. 1210, Philadelphia, PA 19107, USA
e-mail: [Link]@[Link]
Visual Evoked Potential (VEP)
A.V. Levin, M.D., [Link]., F.R.C.S.C. (*)
Pediatric Ophthalmology and Ocular Genetics, Wills Eye Hospital,
Thomas Jefferson University, 840 Walnut Street, Ste. 1210,
VEP can be used to measure visual acuity although the reli-
Philadelphia, PA 19107, USA ability of this technique has been questioned [9]. The data
e-mail: alevin@[Link] depends in part on the type of VEP used [7]. With sweep VEP,

© Springer International Publishing Switzerland 2017 1

A.V. Levin, R.W. Enzenauer (eds.), The Eye in Pediatric Systemic Disease, DOI 10.1007/978-3-319-18389-3_1
2 L.J. Heinmiller and A.V. Levin

Table 1.1  Visual acuity in infants by method [11, 12]

Preferential looking
Method OKN VEP (tellar cards) Otago photoscreener
Full term newborn 20/400 20/100–20/200 20/200–20/545 –
2–3 months 20/400 20/80 20/285 20/20–20/25
4 months 20/200 20/80 20/167 –
5–6 months 20/100 20/20–20/40 20/100–20/120 20/20
1 year 20/60 20/20 20/50 –
OKN optokinetic nystagmus, VEP visual evoked potential

a pattern of vertical lines of varying width move across the 6/9 vision in both eyes [6]. A summary of visual acuity in
visual field in a continuous fashion, usually on a video moni- infants by method can be found in Table 1.1 [11, 12].
tor. As the lines get thinner, they also become proportionately
closer together until the subject can no longer ­perceive that
lines are present. Results of this technique are often reported Contrast Sensitivity
in cycles/degree which must then be approximately translated
into the standard Snellen acuity values (20/x where x = 600/ Contrast Sensitivity begins to develop through the first
cycles/degree). This simple conversion may not be entirely 3 months of life [12]. Fiorentini and coworkers showed that
accurate as it does not take into account other factors such as infants aged 2.5–6 months exhibited contrast sensitivity by
retinal-neural processing and contrast sensitivity. But if one VEP at a mean luminance of 6 and 0.06 cd/m2. They showed
accepts this technique, visual acuities ranging from 20/133 in that scotopic contrast sensitivity develops earlier than phot-
the first month to 20/30 by the end of the first year can be opic contrast sensitivity, and by 4–5 months old are nearly at
found [9]. Norcia and Tyler have cautioned that these values the level of an adult [13]. Contrast sensitivity develops simi-
should be used as the lower boundary of infant performance larly in the central and peripheral visual fields [10].
rather than absolute limits [9]. Further investigations using a
dual-frequency technique VEP in infants 10–39 weeks old
showed that both central and peripheral visual acuity Globe Size
improved by a factor of 2.6 and 2.2 respectively with central
acuity higher by a factor of 2.3 [10]. Axial Length

The axial length of the globe increases in a direct relation-

 urrent Consensus on Ages for Maturity
C ship with age until approximately 8 years old with a stronger
of Visual Acuity correlation for hyperopes as compared to myopes [14]. The
eyeball increases 2.86–3.25 fold between birth and adult-
Depending on which method is used to test visual acuity hood [1, 15]. The most rapid portion of this growth occurs in
there can be large variations in the expected norms through- the first 40 weeks of postnatal life [16]. Stafford and cowork-
out the first years of life (Table 1.1) [11, 12]. ers found the maximum axial length at term, as measured by
ultrasound (A scan), to be 18.6 mm with a mean of 17.0 ± 0.65
standard deviation [17]. Other authors have found similar
Preferential Looking/Tellar Acuity Cards values [16]. Formulas are available for more detailed analy-
sis of the ocular growth patterns [16]. Axial growth of the
Using Tellar Acuity cards, the visual acuity in full-term new- eye occurs in three phases: from birth to 18 months a rapid
borns was estimated at 20/200 [11]. period from mean of 16 to 20.3 mm; a 1.1 mm increase
between years 2 and 5; and 1.3 mm of growth thereafter lev-
eling off at age 13 [18].
Otago Photoscreener

Molteno and coworkers made estimations of visual acuity Saggital, Transverse and Vertical Size
using the Otago photoscreener, a system which uses the vari-
ations in the red reflex to assess fixation, accommodation, At birth, the mean saggital, transverse, and vertical diameters
refractive error, and ocular alignment [6]. They estimated of the globe are 17.5, 17.1, and 16.5 mm respectively repre-
that the visual acuity at 3 months ranges from 6/6 to 6/15, at senting approximately 71 % of the adult equivalents [1]. The
6 months almost 70 % are 6/6 with a further 15 % having anterior segment of the infant globe is roughly 75–80 % that
6/9 in the worse eye, and by 1 year over 90 % have at least of adults. The posterior segment is less than half of the aver-
1  Normal Postnatal Ocular Development 3

9 acuity or worse, or any other objective test result (e.g. visual

Total (cm3)
8.5 Male (cm3) evoked potential, preferential looking) which indicates an
Females (cm3) equivalently significant difference between the eyes.
8

7.5

7 Trend Towards Emmetropia

6.5
In general, there is a trend towards emmetropia throughout
6 early childhood regardless of the initial refractive error [22].
5.5 The main changes towards emmetropia occur in the first
2 years [23, 24]. Further studies have shown that hyperopia
5
decreases with age along with astigmatism found in infants.
4.5 In a prospective study on childhood myopia ranging from
4 −0.25D to −3.50 diopters, Ehrlich and coworkers showed
0-1 yr 1-2 yr 2-5 yr 5-13 yr 13-18 yr that emmetropization was found to occur by 3 years old. The
rate of change in myopia from age 8.5 to 38.5 months occurred
Fig. 1.1  Ocular volume with CT scan in children [21]
at a relatively constant rate of +0.44 diopters per year [25].
Ultimately, emmetropization occurs through a combination
age adult. The total sclera surface in infants averages of passive and active means. Passive means include a growth
822 mm2 which is about 1/3 that of the average adult [19]. in axial length, reduction in the power of the lens, a mild
Therefore, a majority of the change in globe size stems from reduction in power of the cornea as the radius lengthens and a
the expansion of sclera surface in the posterior segment with lengthening of the anterior chamber [26]. The active compo-
50 % of growth occurring in the first 6 months of life, reach- nent relies on the feedback given by the image clarity of the
ing adult averages at around 13 years [19]. retina, for which the exact mechanism is unclear [27].

Volume Spherical Equivalent Anisometropia

Through childhood, the ocular volume increases about In 88.5 % of children, there is no significant difference
300 %; from 2.5 to 7.5 cm3 [20]. Hahn and Chu performed a between the spherical equivalent of the right and left eye [28].
study showing ocular volume measured by CT scan and One group found only 1 % of 519 children less than 48 months
found that rapid eye growth occurs during the first 24 months old to have anisometropia [29]. This group also established
of life and peaks between the ages of 18 and 24 years old 99th percentile curves for normal refraction. They found the
[21]. Figure 1.1 illustrates these findings [21]. range to decrease with age, staying fairly stable after the first
year. In a cross-sectional study of healthy children under the
age of 5 years old, Kuo and coworkers showed that 95 % of
Refractive Error the children had less than 1.50 D of anisometropia [24]. Deng
and Gwiazda measured refractive error in children ages
Cycloplegic Retinoscopy 6 months (n = 1120), 5 years (n = 395) and 12–15 years
(n = 312) and found the mean difference in refraction between
The refractive error of the eye may be measured by a variety the two eyes was similar at 6, 14 months (0.11 D) and 5 years
of techniques. It is standard to use some form of cycloplegic (0.15 D), increasing to 0.28 D at 12–15 years [30]. The preva-
retinoscopy in children. As the differences in the absolute lence of <1.00 D of spherical equivalent anisometropia, was
level of cycloplegia which is obtained through various 1.96 %, 1.27 %, and 5.77 % respectively [30]. Infants with
cycloplegic regimens is small, we will discuss the develop- significant astigmatism (≥1.00 D) in one or both eyes have an
ment of refractive error in the normal infant based on the increased risk of anisometropia (p < 0.05) [30].
reported values obtained through various cycloplegic regi-
mens as if they were equal. However, retinoscopy in infants
and young children without the use of cycloplegia may be Hyperopia
prone to significant error. Data collected under these circum-
stances will not be included. Likewise, the definition of Over the first 3 years of life, the average spherical equivalent
amblyopia may vary between authors. We have chosen as in normal children is −0.75 to +3.00 diopters [28, 31]. Only
our definition a two line difference between each eye based 7–8 % will have hyperopia (farsightedness) in excess of
on projected acuity charts, visual acuity in an eye with 6/9 2.75 diopters during this time period [28, 32] with only 2 %
4 L.J. Heinmiller and A.V. Levin

having greater than 4.00 diopters of hyperopia in the steepest found that oblique cylinder was always a mirror image axes
meridian [32]. Those who have greater than 4 diopters of in the two eyes [29]. The incidence and amount of astigma-
hyperopia at 6 months and stay hyperopic thereafter, have a tism gradually decreases after the first year [28, 32] and may
very high risk of developing accommodative esotropia par- even decrease after the first 4 months [29]. In fact, astigma-
ticularly if there is a family history of strabismus [23]. Kuo tism in excess of 3.00 diopters is uncommon prior to
and coworkers found that greater than 95 % of children less 10 months or beyond 2 years [28]. Only 5.7 % of children
than 5 years old had less than +3.25 diopters of hyperopia will experience astigmatism greater than 2 diopters in the
[24]. One cross sectional study involving almost 10,000 chil- first 3 years of life [28]. The axis of astigmatism is predomi-
dren analyzed risk factors for hyperopia and found that chil- nately (70–90  %) against-the-rule (plus cylinder at axis
dren whose parents had health insurance and a history of 180° ± 15) [22, 28]. With-the-rule astigmatism (plus cylinder
maternal smoking during pregancy were more likely to be at axis 90° ± 15) represents 6–20 % of astigmatism [22, 28].
hyperopic [33]. The relationship between hyperopia and Oblique astigmatism is the least common and accounts for
maternal smoking appears to be linear and dose dependent only 3–8 % of astigmatism in normal children [22, 28]. The
with a 6 % higher prevalence of hyperopia for every increase axis of the two eyes is almost always symmetrical [22]. The
of 10 pack-months of maternal smoking [33]. There was an amount of astigmatism tends to lessen in the first 4 years of
unexpected higher prevalence of hyperopia in 6 year old life, increasing in only 10 % of patients [22]. The etiology of
children as compared to 1–3 year olds [33]. African-­ astigmatism in children is unknown however, like hyperopia,
American children are significantly less at risk for hyperopia maternal smoking during pregnancy was found to be a risk
than non-Hispanic or Hispanic children [33]. factor. Hispanic and African American race, hyperopia and
myopia are all associated with higher incident of astigmatism
[39]. Children with astigmatism are more likely to come from
Myopia families that have an income of <$20,000 per year and lack
vision insurance [39]. The risk for amblyopia in patients with
Myopia (nearsightedness) is unusual in the first year of life. astigmatism as the only variable is only approximately 3 %
In the first 4 years, only 3 % of children are myopic with the although this risk may be as high as 35 % in those children
incidence of myopia being less than 2 % by the age of 5 years with increasing astigmatism in the first 4 years of life [22].
old [29, 34]. Approximately 17 % of children will have up to The risk of amblyopia may also be higher for patients with
4 diopters of myopia with less than 0.5 % having more [32]. oblique axis or higher hyperopic spherical equivalents [22].
Unlike hyperopia, the prevalence of myopia is greater in
children 4–6 years of age compared to those 3 years and
younger [33]. Racial predilection for myopia is strongest in Nasolacrimal System
African-American and Hispanic children when compared to
non-Hispanic white children [33]. There are two main theo- Tears
ries regarding the development of myopia including the
increased demand for near work theory and genetic disposi- At birth tear production is very close to adult levels with pre-
tion theory [26]. The near work theory is supported by the mature infants having a lower rate of both basal and reflex
higher prevalence of myopia in populations with higher edu- tearing [40]. As measured by Schirmer for 5 min with and
cation levels and increased near demands [35, 36]. The without topical anesthetic respectively, the mean basal tear
genetic theory is supported both by the increased prevalence secretion is 6.2 ± 4.5 mm and 7.4 ± 4.8 mm for a cohort of
of myopia in monozygotic twins and increased prevalence of preterm infants between 25.4–37 weeks gestation and 583–
myopia in children with myopic parents [37, 38]. 2700 g whereas for term infants the rates were 9.2 ± 4.3 and
13.2 ± 6.5 [40]. In both groups, the secretion rate was directly
proportional to weight. In term infants, total tear secretion
Astigmatism significantly increased at both 2 and 4 weeks old while in
preterm infants a significant increase in tear production
Most authors have found that the incidence of astigmatism is occurred at 4 weeks [41].
much higher in young children than in adults [28]. In the first
year of life, 19 % of children will have astigmatism [28].
Myopic infants have larger astigmatism which decreases Location of Puncta
with age [25]. The incidence of astigmatism peaks at approx-
imately 25 % between the ages of 7 to 12 months [28]. Over When the lids are closed, the puncta are located 6 mm lateral
the first 4 years of life the incidence is still 25 % [29]. Against to the inner canthus and sit on a mound known as the lacri-
the rule cylinder is more common than with the rule or mal papillae [42]. Upon opening of the lids, the upper punc-
oblique axes (56, 29, and 14 % respectively) [29]. One group tum shifts 0.5 mm nasal to the lower punctum [42]. The
1  Normal Postnatal Ocular Development 5

diameter of the punctum is between 0.2–0.3 mm [42]. The occurs to offset the increase in axial length which is occur-
puncta are normally located medial to the nasal limbus posi- ring the same time therefore resulting in stabilization of the
tioned against the globe in primary position [43]. infant’s refraction [31].
The proximal nasolacrimal system is normally patent at
birth following the normal separation of the eyelids at 7 months
gestation, followed by canalization at the level of the punctum Size
[44]. It has been shown that the last part of the duct to canalize
during development is the valve of Hasner [45]. Incidence of The mean horizontal diameter of the term newborn cornea is
congenital nasolacrimal duct obstruction was found to be 73 % 10.0 mm with a thickness of 0.8 [1]. Stafford and coworkers
in a study reviewing stillbirth fetuses with all obstructions recorded a slightly smaller mean corneal diameter of
being secondary to a mucous membrane at the level of the 9.55 ± 0.5 standard deviation at term [17]. By adulthood, the
inferior meatus [46]. The duct enters the nose within the infe- diameter will have increased to a mean of 12.5 [20]. The
rior meatus under the inferior turbinate 2.5 cm posterior to the thickness is almost 90 % of adult thickness at birth [1].
naris and is approximately 5 mm in length [42].
It should be noted that in children there can be variations
in the distance within the nasolacrimal system secondary to Tactile Corneal Reflex
immaturity. In children, typically the distance between the
canaliculus and nasal floor is 20 mm with adult measure- The tactile cornea reflex is present in at least one eye in only
ments being between 30–40 mm [42]. 10 % of babies at 2 days of age [49]. This increases to 25 %
at 1 week, 50 % at 3.5 weeks, 75 % at 6 weeks, and 100 % by
3 months [49]. Postpartum age is more important in the
Cornea development of this reflex than gestational age [49]. Birth
weight also has a significant positive correlation [49]. This is
Endothelium particularly relevant to corneal protection only if one consid-
ers the developments of the Bell’s phenomenon: 36 % at 1–3
The corneal endothelium in infancy has a regular mosaic pat- days old, 50 % at 4–8 weeks, and 100 % by 4 months [49].
tern of small hexagonal cells although there may be some The corneal reflex is developing more rapidly.
smaller or larger cells and cells with an increased number of
sides [47]. Twinning cells may also be seen [47]. Cell popu-
lation density (CPD) ranges from 2987 to 5624 (mean 4252) Central Corneal Thickness
cells/mm2 in babies less than 1 year of age without a general
pattern of decline over that year [47]. However, infants with Portellinha and coworkers examined 74 newborn infants and
more than 5000 cells/mm2 tend to be less than 2 months old found that the mean central corneal thickness and mean
[47]. The calculated endothelial surface area changes from peripheral corneal thickness was 0.573 ± 0.052 mm and
91.9 to 129.8 mm2 from birth to 1 year of age with an 0.650 ± 0.062 mm respectively [50]. Remon and coworkers
assumed constant growth rate of 3.16 mm2/month [47]. showed an average central corneal thickness of 0.585 ±
Rather than loss of cells, the endothelial cells spread over 0.052 mm in 152 one day old infants. They also measured
this increasing area which may have led some observers to superior, inferior, nasal and temporal peripheral corneal
note a decline in CPD [47]. Clinically, some infant corneas thickness (Table 1.2) finding measurements of
show non-inflammatory retrocorneal particles on the endo- 0.696 ± 0.055  mm, 0.744 ± 0.062  mm, 0.742 ± 0.58  mm, and
thelium which may represent dividing cells [47]. 0.748 ± 0.055 mm respectively [51]. Both studies found the
corneal measurements during the first day of life to be
­significantly higher than the following days of life [50, 51].
Keratometry They failed to find any difference between sex, gestational
age, type of delivery or right and left eyes [50].
The cornea is steeper at birth with progressive flattening Lopez and coworkers found an average CCT in children
towards adult values in the first months of life. At birth, 8 months- to 6 years old of 0.558 mm (0.489–0.614 mm) and
Inagaki found the mean keratometer reading to be 47.00 ± 1.19 for ages 6–17 years 0.560 mm (0.467–0.662) [52]. They
diopters (range 45.69–49.06) [31]. By 1 and 3 months of age failed to find any significant association between CCT and
the cornea has flattened to 46 ± 2.15 and 44 ± 1.70 diopters age [52]. Ehlers and coworkers found that central corneal
respectively [31]. Isenberg and coworkers found the mean thickness reaches adult measurements around 3 years of age
central corneal power to be 48.5 diopters (range 41.4–56.0) [53]. They found an average CCT measurement in children
at birth decreasing to 43.0 diopters (range 41.3–43.1) [48]. It ages 2–4 years old to be 520 ± 0.007 μm and ages 5–9 to be
has been hypothesized that this relatively rapid change 520 ± 0.005  μm [53].
6 L.J. Heinmiller and A.V. Levin

Table 1.2  Infant central and peripheral corneal thickness by age, sex and laterality [51]
Number of subjects CCT SCT ICT NCT TCT
1 day old 108 611 ± 58 713 ± 61 761 ± 69 756 ± 64 760 ± 62
2 days old 114 573 ± 60 686 ± 62 737 ± 72 756 ± 64 744 ± 61
4 days old 20 572 ± 28 691 ± 31 725 ± 35 732 ± 43 738 ± 38
6 days old 16 561 ± 36 681 ± 31 724 ± 34 722 ± 35 731 ± 27
Male 154 598 ± 54 699 ± 59 748 ± 65 744 ± 60 752 ± 58
Female 150 581 ± 50 693 ± 51 740 ± 59 740 ± 56 744 ± 52
Right 152 585 ± 52 694 ± 52 745 ± 64 745 ± 62 748 ± 55
Left 152 585 ± 52 698 ± 58 743 ± 60 739 ± 54 748 ± 55
CCT central corneal thickness, SCT superior corneal thickness, ICT inferior corneal thickness, NCT nasal corneal thickness, TCT temporal corneal
thickness

A recent review of the genetics of central corneal thick- linearly with age [60]. The iridocorneal angle is almost com-
ness looked at the four published studies of the heritability pletely developed at birth although some further recession will
of central corneal thickness including twin and family gradually take place such that the infant’s ciliary body is less
­pedigrees which shows that CCT is one of the most highly visible on gonioscopy than an adults [61]. Kobayashi and
heritable human traits with tremendous variation amongst coworkers showed the trabecular-iris angle in infants from 1 to
different ethnic groups [54]. While there is strong evidence 60 months of age ranged from 15.35 to 44.79° and increases in
that central corneal thickness is genetically driven, no genes angle size correlated positively with an increase in age [60].
have been identified to date [54].

Trabecular Meshwork
Corneal Hysteresis
The normal insertion of the iris and ciliary body at birth is at
Corneal hysteresis is the difference in the pressure required to the level of the scleral spur. As the first year of life pro-
flatten the cornea and the force at which the cornea becomes gresses, a posterior migration occurs forming the angle
flat again which is a direct measurement of the biomechanical recess. Additionally, the endothelium that lines the angle
properties of the cornea [55]. Kirwan and coworkers studied becomes fenestrated while an endothelial layer of cells
91 normal eyes of 42 children and found mean corneal hyster- migrates into the underlying uveal meshwork [62]. The uveal
esis of 12.5 mmHg. There was no correlation between age and trabecular meshwork are relatively transparent at birth,
and corneal hysteresis [56]. In a separate study, Kirwan found becoming more pigmented through the first year of life [63].
the average adult hysteresis was 10.8 ± 1.5 mmHg indicating While iris processes are rarely present, they are either faintly
corneal hysteresis reduces with age from childhood to adult- pigmented or nonpigmented [64]. The trabecular meshwork
hood [57]. Ortiz et al. found a mean corneal hysteresis of has been described as a “moist,” transparent membrane and
10.8 ± 1.5 mmHg in 165 eyes and found hysteresis to be lower appears somewhat translucent [65]. The peripheral iris
in older eyes with the difference between the younger group appears to be more flat and thin than seen in adults [62]. By
(9–34 years) and oldest group (60–80 years) to be statistically 1 year old, the trabecular development is complete [64–66].
significant [58]. Lim and colleagues noted that in a study of
257 healthy patients (age 13.97 ± 0.9 years) in the Singapore
Cohort Study, that corneal hysteresis (11.80 + 1.55 mmHg) Intraocular Pressure (IOP)
and corneal resistance factor (11.83 + 1.72 mmHg) are associ-
ated with narrower retinal arterioles [59].  alues Goldman Vs. Pneumotonometry Vs.
V
I-Care® Vs. Tono-Pen® Vs. Perkins

Anterior Chamber Stafford and coworkers found a mean IOP of 15.2 ± 3.4 at

term [17]. Giles produced higher values while using a
Depth Schiotz tonometer to measure intraocular pressures in 32
babies less than 1 h old and found the pressure approaches
Although the newborn anterior chamber often appears rela- the upper limit of adult normal levels with 25.8 mmHg used
tively shallow, the depth is almost 75 % of adult values [1]. as the upper limit of normal [67]. Six infants exceeded this
Kobayashi and coworkers evaluated the anterior chamber of level while none had measurements exceeding 30.4 mmHg
46 infants age 1–60 months and showed average anterior [67]. Radtke and Cohan used a Perkins tonometer on 60
chamber depth was 1.724–3.743 mm with depth increasing infants between 19 and 173 h of age and found a mean IOP
1  Normal Postnatal Ocular Development 7

Table 1.3  Infant intraocular pressure studies [68, 70–74]

Intraocular
Method by which pressure (mmHg) Number of
Author Anesthesia pressure obtained mean (range) Patient age measurements
Hörven [70] Topical Schiotz 16.3 (10.2–24) 4 h–10 days 50 infants (60 attempts)
Kornblueth and assoc [71] Diethyl ether Schiotz 22.5RE, 20.9LE 5–24 h 47 eyes
(15.9–29)
Westby and Skulberg [72] Diethyl ether Schiotz 16.9 (8.5–22.4) 1.5–9 years 110 eyes
Hetherington and Shaffer [73] Fluothane Draeger and Schiotz 12.5 (7–22) 3 months–7 years 30 eyes
Sampaolesi [74] Methoxyflurane Goldmann and Draeger 10 (7.81–12.19) Few days–5 years 85 eyes

16
Females
Normal values may depend on the measurement method.
Males One group found that the normal values using Goldmann
15 applanation tonometry on children less than 10 years old fol-
lowed the formula IOP = (0.71 × age in years) + 10 whereas
14
the linear fit worsened after the first decade when the mean
IOP was 14.6 ± 3.3 [80]. Using pneumotonometry, the same
13
authors found no age related effects with a mean IOP of
12 16.8 − 3. They showed that for all ages the IOP by Goldmann
was approximately equal to 1 + (pneumotonometer × 0.78).
11 After 10 years a more accurate estimation was IOP by
Goldmann = (0.94 × pneumotonometer value) − 1.2. Under
10 general anesthesia (agent not specified) they found that read-
ings by Perkins tonometer = 2.6 log (age) + pneumatonome-
15 yr
11 yr

-1 r
13 yr
14 yr

yr
2- r

10 0 yr
5- r
3- r
4- r

7- r

9- yr
6- r

8- r

12 2 y
y

y
y
y

y
y

5
1

3
4

6
2

5
3
4

9
6

-1
-1
-1

-1

-1
1-

ter value − 10.3. Percentile charts are available in their paper.

1

They conclude that normal adult values for IOP are reached
Fig. 1.2  Mean tonometric readings (in mmHg) by sex and age [76, 77] by 10 years of age. Below this age they theorize that the
lower measured values are actually artifacts due to the differ-
of 11.4 + 2.4 mmHg (range 6–17) [68, 69]. A summary of ence in ocular wall rigidity. Johnson and collegues showed
other studies of infant intraocular pressures can be found in that intraocular pressures are significantly lower when suc-
Table 1.3 [68, 70–74]. cinyl choline is used during induction which is thought to be
By the second decade, there is no significant difference related to a temporary increase in outflow [81].
between mean IOP in the sitting (16 ± 2.4 mmHg) or supine Other options for intraocular pressure measurements
(17  ± 2.3 mmHg) position as compared to adults over include the Tono-Pen® and ICare® rebound tonometer. In a
20 years [75]. Values for tonometric readings by sex and age study of 39 children ages 3–18 months old using the
found by Pensiero and colleagues [76] using the noncontact ICare tonometer, the average intraocular pressure was
Keeler Pulsair tonometer and Youn and colleagues [77] using 11.82 ± 2.67 mm with a median value of 10 mmHg with a
the Perkins tonometer can be found in Fig. 1.2. range of 7.3–17.0 mmHg [82]. Bordon and coworkers com-
These findings were used to break the increase in intraocular pared IOP in children with several different methods and con-
pressure in children into three groups. First, the neonatal phase cluded that the Tono-Pen is reliable in children as there was no
with average value of 9.59 + 2.3 mm followed by an exponen- statistically significance compared to Perkins (P > .05) [83].
tial phase up to age 7–8 years and finishing with a gradual When evaluating the Schiötz measurements it was shown
steadying of eye pressures until the 16th year of life [76]. Jaafar these values were significantly higher than those obtained with
and Kazi utilized regression analysis to show IOP of children the Perkins and the Tono-pen tonometers (P < .05). Schiötz is
and adults are equal using Perkins tonometry by age 12 [78]. an undesirable method for measuring IOP in children [83].
Using Perkins tonometry, IOP increases gradually from infants
(4.55 + 0.51 mmHg age 0–1 year) to children (7.85 + 1.27 mmHg
by age 4–5 years) to adults (13.21 + 2.11 mmHg) however, there Pupils
was no statistically significant different when measuring IOP
with pneumotonometry [78]. Sihota and colleagues also noted in Size
their study of 810 eyes in 405 patients ranging in age from 0 to
12 years that IOP reached adults levels by age 12 and found that The pupillary size of newborns and infants is generally
IOP correlated directly with refraction (r = 0.69) and pachymetry smaller than that of adults [84]. Average pupil sizes in neo-
(r = 0.39) and inversely with axial length (r = −0.1) [79]. nates of 3.8 ± 0.8 mm with a range of 1.5–6 mm have been
8 L.J. Heinmiller and A.V. Levin

reported [84]. Wilmer and Scammon calculated that the Iris

mean pupillary size of neonates was 70 % of adult size [1].
Pupil size is significantly larger in the presence of a blue iris Color
(4.07 ± 0.92) as compared to neonates with brown irides
(3.64 ± 0.74) [84]. There are several factors that have been In general, the newborn iris is paler than in older children
proposed to account for the smaller pupil in an infant. These [90]. At birth, when not controlled for race, 39 % of babies
include smaller anterior segment dimensions, loss of central have blue irides with the remainder having brown irides [84].
inhibitory impulses to the oculomotor nucleus in a more con- In more darkly pigmented races, the iris has a darker appear-
stant state of sleep and a poorly developed iris dilator muscle ance at birth due to a greater number of stromal melanocytes
[85–87]. In addition, pupil size may also be affected by the [90]. In all races, the iris darkens during the first 6 months of
presence of quality of fixation, refractive error, amblyopia, life due to increasing maturation of melanocytes [90]. Lighter
and strabismus [6]. colored irides may appear more vascular in the neonatal
period [90]. The Louisville twin study evaluated eye color in
monozygotic and dizygotic twins and showed that by 6 years
Anisocoria of age, most individuals achieve stable eye color. They did
find a subpopulation of 10–15 % of Caucasian subjects who
A difference of greater than 0.4 mm between the two eyes is continue to have changes in eye color throughout adolescence
a common finding in the normal population. At birth, 21 % of and adulthood thought to reflect changes in melanin content
term neonates demonstrate physiologic anisocoria [84]. or distribution [91]. The study further illustrated the genetic
There is no significant change in this rate based on iris color influence on iris color as concordance was high (90 %) among
[84]. Roarty found that no term neonate had anisocoria of monozygotic twins and declined among dizygotic twins from
greater than 1.2 mm and 97 % of babies with anisocoria had 80 % at 3 months old to 50 % by 6 years old [91].
less than 1 mm difference between their two eyes [84].

Structure
Red Reflex
Iris crypts are not fully developed at birth [90]. Although
The red reflex is one of the most important screening tech- this process continues for several months after birth, little
niques for neonates and infants as it may reveal the presence maturation occurs in the first 2 weeks of life [90]. Although
of abnormalities along the visual axis, pupillary abnormali- Purtscher originally felt otherwise, there appears to be no
ties, refractive errors, or strabismus [6]. When normal fixa- difference in crypt development related to iris color [90].
tion and focusing occurs, the red reflex darkens to a dull One group of researchers found that iris vascularity and
homogeneous orange red color [6]. In neonates who fixate crypt development were greater in males [90]. The infant iris
but do not accommodate properly (see above), the reflex will is flatter and thinner than the average adult. Iris thickness
appear brilliant yellow or almost white [6]. A thin circle may evaluated at the thickest part of the iris measured 249–
also be seen normally within the red reflex [6]. However, if 579 μm in infants age 1–60 months and correlated positively
the reflex is not homogeneous or particularly when it is with age [60].
asymmetric between the two eyes, further investigation is
warranted. A black or comparatively darkened reflex may
indicate obstruction of the visual axis or ocular misalign- Lens
ment. Abnormal comparative unilateral “brightening” may
be a sign of reduced visual acuity in that eye [6]. Diameter

At birth, the horizontal lens diameter is approximately 6 mm

Responses and continues to progress as illustrated in Fig. 1.3 [20, 92,
93]. The period of most rapid growth occurs in the first
Isenberg and coworkers found that pupillary response was 2 years of life with moderate growth until age 4 and only a
consistently present in 99 % of the infants studied if gesta- small amount of growth after age 5 [92]. The adolescent lens,
tional age was >31 weeks [86]. In the full term neonate, con- with a diameter of 9–9.5 mm, is not yet at the same diameter
vergence is variable with accurate and maintained of the adult lens which keeps increasing well into the final
convergence becoming well developed by 2–3 months old decades of life with an associated decrease in anterior lens
[88]. The appearance of the direct and consensual light curvature [94]. As the lens gets bigger, the distance between
reflexes occurs 30 weeks after conception [89]. the lens edge and the ciliary sulcus decreases [94].
1  Normal Postnatal Ocular Development 9

25
capsular thickness at Anterior Pole
16 years 9.3mm capsular thickness at insertion of zonules
capsular thickness at the equator
20
2-5 years 8.5mm

15
6-9 months 7.6mm

10
3 months 7.1mm

2 months 6.8mm 5

0
Birth 6mm
Neonatal Young Adult (11-20yr) Old Adult (61-70yr)

Fig. 1.4  Thickness of the anterior lens capsule by location (mean in

μm) [99]
Fig. 1.3  Mean crystalline lens diameter (in mm) by age [20, 93, 96]

The thickness of the human lens has been measured in

numerous studies and found to be 3.5–6.5 mm in the new- Rate of growth (mg/year2)
born, and 3.73–4.6 mm at 20–40 years old [95]. Using ultra- 200
Rate of growth (mg/year2)
sound, Larsen evaluated lens thickness from birth until 180
puberty and found that the mean thickness of the lens 160
decreases by 0.3 mm in the first year of life then by another 140
0.2 mm per year until leveling off at 8–10 years old [18]. 120
100
80
Bag Size 60
40

The lens capsule remodels throughout life as the volume of 20

0
the lens increases [96]. Changes to the posterior lens capsule
are negligible following birth, while the anterior lens epithe-
s

rs
s

s
ay

th

ar

ea
0d

on

ye

lium continues to secrete anterior capsule [96]. At birth, the 0y

15

10

-9
11
7-

s-

10

mean diameter of the capsular bag is 7.0–7.5 mm and

0-

th
on

increases to about 9.0–9.5 mm by age 2 [97]. These values

m
11

support the findings of Ohami and coworkers and Richburg

and Sun who measured the capsular bag to be about 1 mm Fig. 1.5  Lens weight from birth to adulthood [96]
larger than lens diameter [27, 98]. There is also a change in
capsular thickness with age (Fig. 1.4) [99].
When viewed with electron microscopy, the lens capsule
consists of a combination of type IV collagen, as well as, Weight
types I and III collagen, laminin and fibronectin [100]. The
infant anterior capsule is highly elastic in nature when com- Figure 1.5 displays the change in lens weight with age [96].
pared to the adult capsule [100]. Krag and coworkers looked
at the extensibility of the capsule throughout life and found
its maximum extensibility was in infancy and decreased by Power
0.5 % every year throughout life [101]. While extensibility
decreases by at least a factor of two, overall strength At birth, the accommodative power of the lens is between 14
decreased by a factor of five [101]. and 16 diopters and then decreases with age (Fig. 1.6) [102].
10 L.J. Heinmiller and A.V. Levin

Fig. 1.6  Accommodation by Mean Maximum Accommodative response

age measured by dynamic (in diopters)
retinoscopy [102]
14

13

12

11

10

7
3-5 yr 6-7 yr 8-10 yr 11-15 yr 16-19 yr 20-26 yr 27-35 yr

Zonular Insertions
Ciliary Body
The zonules insert less anteriorly on the lens of an adolescent
as compared to adults [94]. The distance between the ante- Measurements Pars Plana and Plica
rior zonular insertion and the lens edge is approximately
0.75–1 mm with a zonular free central anterior zone on the The lengths of the pars plicata and pars plana at different ages
anterior capsule of 6 mm in infancy which increases to are summarized in Table 1.4 [107]. The pars plana represents
7–9 mm s in adolescence [20, 94]. Fetal and infantile eyes 73–75 % of the total ciliary body length in infants and young
have zonular fibers that are finer, less aggregated and exhibit children. The ciliary body is 76 % of adult size by 2 years old.
considerably more proteoglycan staining with Alcain blue or Procedures designed to enter the posterior segment of the eye
cuprolinic blue than in adult eyes [103, 104]. The loss of size via the pars plana must therefore be appropriately adjusted so
that occurs with aging has been suggested to be the result of as to avoid unplanned violation of either the ciliary body or
decreased fibrillin synthesis with age, which is also seen in retina. Similar to the adult population, the temporal ciliary
the aging aorta [105]. The flat zonular insertional areas attach body is longer than the nasal ciliary body in the pediatric age
to the thin lens equator at its periphery with the zonular bun- group [107]. The anterior two thirds of the ciliary body houses
dles appearing closely packed and thick for the first two the largest portion of the ciliary muscle with a few fibers pass-
decades of life [104]. These areas of insertion become wid- ing posteriorly to the ora serrata [107]. In the young eye, the
ened and displaced more centrally as the lens grows in diam- connective tissue between these muscle fibers is scarce [107].
eter and thickness [104].

Retina
Resolution of  Tunica Vasculosa
The retina is not fully mature at birth. During the ninth month
The tunica vasculosa lentis is the anterior portion of the hya- of gestation, the amount of the differentiated retina increases
loid vascular network that surrounds and supplies the grow- considerably, the retinal vessels extend to the ora serrata, the
ing lens in utero [63]. The tunica is made up of multiple macula continues to differentiate with the foveolar reflex
different vascular sources including the hyaloid artery, the appearing as the foveolar depression forms [108]. Although
vasa hyaloidae propria and from the anterior ciliary vessels mitotic activity during prenatal development stops at
by way of the major arterial circle of the iris [106]. The 30 weeks gestation, the surface area of the retina continues to
development of the tunica peaks at 10 weeks gestation and increase at a rate of 10–15 mm2 per week for the first 3 weeks
regresses during the fourth month of gestation [63]. Complete after birth secondary to growth and maturation of individual
regression occurs in stages with the posterior part (supplied cells [109]. The globe also continues to develop with the dis-
by hyaloids system) regressing completely by the seventh tance between the equator and ora enlarging until the age of
month of gestation and the anterior part (supplied by ciliary 2 years old. The neonatal retina is thinner (120–150 μ) than
system) regressing completely by the 8 month of gestation that of an older child or adult (160–200 μ) [6]. Several stud-
[106]. Occasionally, the tunica vasculosa lentis fails to com- ies in infants have shown that while the macular region is
pletely resolve leaving a small, 1–2 mm, area of fibrosis immature the peripheral region seemed to resemble that of
termed a Mittendorf dot on the back of the lens [63]. the adult [110].
1  Normal Postnatal Ocular Development 11

Table 1.4  Postnatal development of the ciliary body [107]

Mean length nasal pars Mean length temporal Percentage of adult length Percentage of adult length
Age plicata (range in mm) pars plicata (range in mm) nasal ciliary body (%) temporal ciliary body (%)
7 days–6 months 3.06 mm (2.60–3.45 mm) 3.31 mm (2.80–4.30 mm) 64 57
6–12 months 3.54 mm (2.86–4.45 mm) 3.85 mm (3.10–4.56 mm) 74 67
12–24 months 3.87 mm (3.28–4.48 mm) 4.14 mm (3.46–4.99 mm) 81 72
24–72 months 4.28 mm (3.75–4.95 mm) 4.94 mm (4.15–5.50 mm) 90 85

By the fifth to eighth day of life the photoreceptors of the Table 1.5  Macular volume and thickness variation by age and race [114]
macula have elongated basal axons causing the photoreceptor 3–6 years old 7–10 years old 11–17 years old
layer to become much thicker than in the prenatal retina [111]. Mean macular volume (mm3):
At birth, the rod inner segments have already reached their All 6.99 6.96 6.91
adult width of 2 μm, the inner segments of the cones are unta- White 6.96 6.94 6.93 (p = 0.03)
pered and both rod and cone inner and outer segments are Black 6.87 6.84 6.87
30–50 % of adult length [111]. The cone outer segments elon- Mean foveal thickness (μm):
gate up to the age of 5 years old and rod outer segments up to All 186 196 192
13 years old [111]. At birth, the rod and cone length varies White 198 196 200 (p < .001)
Black 176 176 183
depending on location in the retina as the mid-­peripheral inner
segments are slightly longer and outer segments are 50 % lon-
ger than in the parafoveal retina [111]. By 5 years old, the tors in visual development including outer segment length
mid-peripheral rod outer segments are only slightly longer and cone packing density are only half the adult values at
than in the parafoveal region with little change occurring 45 months of age [112]. The capillary free zone in the infant
throughout the remainder of life [111]. The photoreceptors in is similar in size to that of the adult [113].
peripheral retina develop earlier than those in the central ret- El-Dairi and coworkers evaluated variation in macular
ina and parafoveal photoreceptors develop in advance of thickness and volume with age and race (white vs. black) in
foveal cones suggesting that peripheral retinal regions are uti- children ages 3–17 years (Table 1.5) [114]. They found that
lized more in the neonate before foveal cone vision becomes perifoveolar retinal thickness and foveal thickness were both
dominant [111]. The elongation of the fibers of Henle contrib- significantly greater in white than in black children as were
ute to growth of the outer plexiform layer up to the 45th month measurements of total macular volume [114]. These racial
of post gestational life [111]. The inner retina has a different differences were more significant in the two younger age
path to maturity being almost adult like at birth [111]. groups, 3–6 year olds and 7–10 year olds, while only the
fovea was significantly thicker in white children than black
children in the older group, 11–17 year olds [114]. Huynh and
Macula coworkers studied children (mean age 6.7 years) and found a
mean minimum foveal thickness of 161.1 (±19.4) μm, and
After birth, the fovea continues to differentiate for the first mean thickness measurements of the central, inner, and outer
45 months of life [108]. From birth until 15 months old, the macula of 193.6 (±17.9), 264.3 (±15.2), and 236.9 (±13.6)
fovea continues to deepen as a result of the migration of cells μm, respectively [115]. They found that the temporal quad-
in the inner retina toward the periphery [112]. The foveola, rant was thinner than other quadrants in both the inner and
which measures over 1000 μm at birth, becomes progres- outer macular regions. Total macular volume was also nor-
sively more narrow due to the central migration of cones mally distributed, with a mean of 6.9 (±0.4) mm3 [115].
reaching the adult diameter of 650–700 μm by 45 months Variations in sex and ethnicity were observed with thicker
old. It has been determined that this immature foveola measurements for the foveal minimum, central, and inner
accounts for 5° of visual angle [110]. This results in an macula in white compared to East Asian children as well as in
increase in foveolar cone density from 18 cones/100 μm at boys compared to girls [115]. Measurements of the outer
1 week postnatal to 42 cones/100 μm in the adult [112]. macular thickness showed no significant gender-ethnic differ-
Elongation, maturation and an increase in packing density ences [115]. Changes in thickness based on axial length and
occurs in the development of the foveolar cones with cone spherical equivalent were noted in the inner and outer macula,
diameter going from 7.5 μm at 5 days postnatal to 2 μm by but not in the central macula [115]. These changes include
45 months [112]. During this time the foveolar cones develop significant thinning with increasing axial length and signifi-
both outer segments and basal axon processes. While foveo- cantly thicker measurements with more hyperopic spherical
lar differentiation is complete at 45 months of age, key fac- equivalent [115]. Huynh and coworkers went on to evaluate
12 L.J. Heinmiller and A.V. Levin

older children ages 11–14 years and found mean (SD) thick- and b-wave amplitude/log intensity (V/log I) curve in 62
ness of the central 1 mm, and inner and outer macular rings to children ages 10 days to 15 years old, and 30 individuals
be 197.4 ± 18.7, 271.9 ± 15.0, and 239.5 ± 13.5  μm, respec- 15–37 years old [120]. They determined that by 3 to 5 years
tively with a foveal minimum thickness of 161.6 ± 19.9 μm old, dark- and light-adapted ERG a- and b-wave amplitudes
[116]. Minimal differences between sexes were noted [116]. reached adult levels recognizing that b-wave amplitudes of
scotopic rod-mediated responses were slower to reach matu-
rity than mixed rod-cone mediated responses [120]. While in
Vascularization early infancy oscillatory potentials were the most immature
of the ERG responses, the rate of development exceeded the
Retinal vascular development is complete first in the nasal rate of development in other responses allowing adult ampli-
retina around the eighth month of gestation but the temporal tudes to be reached by 2 years old [120].
retina may continue to develop through the first few weeks
of life, with avascular retina relying on choroidal circulation
for nourishment [63]. Stone and coworkers have shown that Vitreous
in animal studies, vascular endothelial growth factor (VEGF)
is expressed in the developing neural retina by astrocytes in Hyaloid Remnants
the inner surface and in Müller cells of the inner nuclear
layer [117]. It was also shown that VEGF expression in the The incidence of visible hyaloid remnants in the term infant
inner nuclear layer closely precedes the formation of the has been estimated at around 3 % [121]. Hyaloid remnants
superficial and deep retinal vessels [117]. VEGF expression may be visible by B-scan ultrasonography even when noth-
by the retinal pigment epithelium lacks temporal and spatial ing is visible ophthalmoscopically [122]. These remnants are
proximity to the normal development of retinal vessels sug- often bloodless but may be a cause of vitreous hemorrhage if
gesting that it does not play a role in the retinal vasculature blood-filled and associated with persistent hyperplastic pri-
but may be important in the choroidal circulation [117]. mary vitreous, coloboma of the optic disc, optic nerve hypo-
plasia or posterior vitreous cysts [123, 124]. Remnants are
more often in seen in eyes with shorter axial lengths [122].
Electroretinography (ERG)

Age related normative values for retinal function in children Characteristics

based on electroretinogram (ERG) studies have been estab-
lished (although the data of Birch and Anderson may not The vitreous is composed of collagen fibrils including types
apply to non-caucasian children with more darkly pigmented II, VI, IX, and a hybrid V/XI, glycosaminoglycans such as
retinas) [118]. It is important that comparisons of patient val- hyaluronan, two forms of chondroitin sulfate proteoglycan,
ues to such normative data must be conducted using identical the proteoglycan heparin sulfate, and non-collagenous struc-
standard ERG protocols [118]. tural proteins including fibrillin and opticin [108]. Type II
Males have slightly lower retinal responsiveness than collagen accounts for 75 % of the collagen found in the vitre-
females of the same age [118]. Rod, cone, and cone 30-Hz ous [108]. The dense concentration of collagen at birth gives
flicker responses can all be documented at 36 weeks post-­ a darken appearance on dark-field slit-microscopy, but total
conception [118]. Rod responses are barely detectable at collagen content in the vitreous decreases throughout the
birth (average amplitude 2.7 μV) but develop rapidly in the first several years of life until the third decade [125].
first 4 months of life [118]. Cone responses show a similar Hyaluronan is not present in the infant at birth but is pro-
but less dramatic increase [118]. By 4 months old the retinal duced in the eye, possibly by Müller cells or the ciliary body,
responses are more than half normal adult values [118]. and given its hydrophilic composition, causing swelling in
Rodriguez—Saez and coworkers looked at 296 eyes from the vitreous allowing the collagen fibrils to separate produc-
148 healthy subjects ages 1 week to 21 years old and found ing less light scatter on dark-field microscopy and contribut-
that most of the developmental changes in the ERG occur in ing to the overall growth of the eye [108].
the first 6 months of life with the a wave completing its
development at 3 years old and the b component showing a
smooth, gradual increase in latency between 3 and 18–21 Attachments
years old and amplitude from 7–8 to 12–14 years old [119].
Westall and coworkers also examined the development of The vitreous is firmly attached to several structures in
ERG specifically measuring rod response, maximal response, the eye including the ciliary epithelial cells and the inner
oscillatory potentials (OPs), cone response, flicker response, limiting membrane of the retina at the ora serrata [126].
1  Normal Postnatal Ocular Development 13

Several studies have shown that heavy bundles in the vitre- erative changes seem to be less severe than in adults [20].
ous base intertwine strongly with retinal glial cells in the Infant sclera has approximately one half the tensile strength
peripheral retina [126, 127]. In the posterior fundus, the vit- and four times the pliability of adults [132]. The coefficient of
reous fibrils blend into the fibrillary material of the inner stretching is 0.6 times that of an adult which gives the infant
limiting membrane lamina which is very thick in this region sclera more elasticity [106].
of the fundus [128]. The peripheral shell of the vitreous (vit-
reous cortex) arises from the anterior vitreous forming the
anterior hyaloid face which sits 1.5 mm anterior to the ora Thickness
serrata, as well as coursing posteriorly from the posterior
vitreous base to form the posterior cortex [108]. Zonular The sclera is composed of three different proteoglycans
fibers have also been found extending posteriorly within including aggrecan, biglycan, and decorin, which undergo
1.5 mm of the ora serrata [129]. The interface between the structural changes responsible for an increase in sclera thick-
posterior vitreous and retina is extremely strong in children ness from 0.45 mm in neonates to 1.09 mm in adults [26].
secondary to the unique insertion of vitreous cortex colla-
gen fibrils into the basal laminae of the retina making the
practice of separating these layer surgically virtually impos- Optic Nerve
sible [108]. Light microscopy and electron microscopy
evaluation of the vitreo-retinal interface show that the fibrils Width
uniting retinal cells and vitreous have the same appearance
in the human fetus as in the peripheral one third of the adult The number of axons increase rapidly during the first
retina [126]. The union between vitreous cortical fibrils and 10 weeks of embryonic life, peak at 3.7 million (double that
inner limiting membrane are visible in eyes under the age of of the average adult), then enter a 3 week period in which the
twenty but these unions become difficult to demonstrate number remains constant after which, a rapid decrease in the
posterior to the anterior third of the retina after this age number of axons occurs [133]. Specifically, the number of
[126]. In 40 % of eyes from individuals less than 20 years axons peaks then drops to the adult value of to 1.1 million
old, scanning electron microscopy of vitreous cortex shows (average adult value) by 30 weeks gestation. While the initial
adherence to the macula, temporal arcades and peripapillary number of axons may determine disc size, the number of
posterior pole with ultrastructural studies showing inner axons lost may dictate cup size. Hellström and coworkers
portions of Muller cells attached to the posterior internal looked at optic nerves in healthy children ages 2.9–9.1 years
limiting lamina [130]. These findings suggest the connec- old and found the median optic disc area was 2.87 mm2
tion between Muller cells and the internal limiting lamina (range 2.04–4.02) with no increase in optic disc area with
are weaker than adhesions between vitreous cortex and age [134]. This finding supports that reported by Mansour
internal limiting lamina [130]. showing no change in optic disc area in normal children ages
2–10 years old [135]. Rimmer and coworkers looked at
autopsy eyes from patients ages 4.8 months gestation to
Sclera 21.9 years and found that 50 % of the growth in the optic disk
is complete at 20 weeks of gestation, 75 % by birth and 95 %
Rigidity before 1 year of age [136]. Optic nerve vertical diameter was
found to be greater than horizontal diameter in all age groups
The sclera is less rigid in childhood which results in “collapse” [136]. Table 1.6 illustrates mean vertical and horizontal
during intraocular procedures such as cataract extraction or diameters and area of the optic disc by age group [136, 137].
trabeculectomy, although the consequences of theses intraop- One important note is that the autopsy eyes were fixed in

Table 1.6  Mean vertical and horizontal diameters and area of both the optic disc by age group [136, 137]
Term to 6 months old 6 months to 2 years old 2–10 years old >10 years old 42.7 (±19.6) years old
Mean vertical diameter 1.37 ± 0.21 1.57 ± 0.15 1.64 ± 0.20 1.73 ± 0.23 1.92 ± 0.29
optic disc (mm ± SD)
Mean horizontal 1.13 ± 0.19 1.40 ± 0.17 1.43 ± 0.19 1.59 ± 0.21 1.76 ± 0.31
diameter optic disc
(mm ± SD)
Mean area of optic 1.25 ± 0.40 1.73 ± 0.32 1.87 ± 0.44 2.19 ± 0.54 2.69 ± 0.70
disc (mm2 ± SD)
14 L.J. Heinmiller and A.V. Levin

formalin which, based on prior studies, may cause NFL Thickness

­approximately 12–13 % optic nerve shrinkage. After adjust-
ing for this fixation artifact, the measurements match those Various studies have evaluated the average retinal nerve fiber
of clinical studies [136, 138]. layer in different races and ages (Table 1.7) [114, 115, 126,
Imaging of newborn optic nerve heads using Optical 143–145].
Coherence Tomography (OCT) found a mean optic disc area El-Dairi and coworkers found that measurements of
of 1.26 ± 0.23  mm2 with a mean vertical diameter of RNFL thickness were not dependent on age in children
1.37  ± 0.15 mm and a mean horizontal diameter of younger than 18 years which is compatible with other pub-
1.14 ± 0.12  mm [139]. The vertical diameter of the optic disc lished studies in children [114]. These measurements
was significantly longer than the horizontal diameter remained stable in adults [114]. In a study of 357 Caucasian
(p < 0.0001). Birth weight and sex did not influence the size children aged 9.16 ± 1.7 years, Elía and colleagues also found
of the optic disc [139]. no difference in any of the parameters tested including mean
The Sydney Childhood Eye Study provided measure- RNFL thickness (98.46 ± 10.79 mm) with regard to weight,
ments for optic nerve head dimensions based on OCT and height and gender [141]. They noted the temporal quandrant
digital photographic planimetry in healthy 6 year olds and contained the thinnest RNFL (69.35 ± 11.28 mm), followed
found mean planimetric optic disc area was 2.29 mm2 (CI by the nasal (71.30 ± 13.45 mm), superior (123.65 ± 19.49 mm)
2.27 to 2.32), mean cup area 0.48 mm2 (CI 0.47 to 0.50), and inferior (130.18  ± 18.13 mm) quadrants [141]. The
mean vertical disc diameter 1.81 mm (CI 1.80 to 1.82) and authors also failed to demonstrate any statistically significant
mean vertical cup diameter 0.72 mm (CI 0.71 to 0.73), change in the RNFL or optic nerve head parameters with
resulting in a mean vertical cup/disc ratio of 0.40 (CI 0.39 increasing age, a finding also reported by others [114, 140,
to 0.40) [140]. This finding is similar to another study in 143, 144]. Other considerations in children include a proven
slightly older children (9.16 ± 1.7 years) using OCT that variation in optic nerve head parameters based on ethnicity
found an average cup/disc ratio of 0.43 (SD 0.19) [141]. as well as variations in measurements among different com-
Richardson utilized direct ophthalmoscopy to evaluate the mercially available imaging devices [144].
incidence of cup to disc asymmetry in 483 normal new-
born infants and found an incidence of 0.6 % with only
2.6 % of the infants having optic cups >1/3 the disc diam- Optic Nerve Sheath
eter [142].
Comparisons could be made between measurements Ballantyne and coworkers evaluated optic nerve sheath diam-
made by planimetry and optical coherence tomography for eter measurements in 102 normal children and found the
vertical, horizontal and area cup/disc ratios (p > 0.05), but range was 2.1–4.3 mm with a mean of 3.1 (SD 0.36) mm
only for vertical disc diameters between 1.75 and 1.96 mm. [145]. By adulthood, the retro-orbital optic nerve sheath
They also reported prevalence of various optic nerve find- width reaches 5.5 ± 0.8 mm just behind the globe and 4.2 ± 0.6
ings including visible lamina cribrosa pores in 4.9 % (associ- at its midsection in the orbit [146]. A relation between increas-
ated with larger optic nerve parameters), optic disc tilt in ing age and increasing optic nerve sheath diameter (r2 = 0.48)
1.6 %, cyclotorsion in 8.7 %, and cilioretinal arteries in 27 % was noted, with the greatest increase in the first year of life
(with tendency for temporal location). After adjusting for [145]. Under 1 year old the mean optic nerve sheath diameter
age, sex and ethnicity, neither α-peripapillary atrophy nor was 2.9 mm (range 2.2–3.4 mm, SD 0.4) and over 1 year old
β-peripapillary atrophy was associated with myopia, 3.1 mm (range 2.3–4.0 mm, SD 0.3, p = 0.01). Based on this
although eyes with b-peripapillary atrophy had a longer data, the upper limit of normal was defined as 4.0 mm for
mean axial length (p < 0.04). those under 1 year old and 4.5 mm for older children [145].

Table 1.7  Studies of retinal nerve fiber layer thickness by optical coherence tomography [114, 115, 126, 143–145]
Source El-Dairi et al. Salchow et al. Huyhn et al. Ahn et al. Parikh et al.
Race/ethnicity Black 92 % Hispanic White Korean Asian Indian
White East Asian
Age mean (range) 8.5 (3–17) All 9.7 (4–17) 6.7 (6, 7) White 12.6 (9–18) 11.1 (5–20)
8.6 (3–17) Black 6.7 (6, 7) East Asian
8.5 (3–17) White
Mean average 108.27 (98.8) All 107 (11.1) 102.7 White 105.53 (10.33) 100.15 (10.8)
RNFL in μm (SD) 110.7 (8.84) Black 107.7 East Asian
105.9 (10.18) White
RNFL retinal nerve fiber layer
1  Normal Postnatal Ocular Development 15

Blood Flow measurements throughout childhood can be found in

Table 1.8 [19, 146]. Muscle width values may differ between
Flow Supine Vs. Sitting CT scan and ultrasound measurements [148]. Comparatively,
infant medial rectus muscles measure 7.9 mm in width and
There has been very little research into ocular blood flow the lateral rectus muscle measures 6.9 mm in width [149].
during childhood. Ravalico and coworkers measured pulsa- Swan and Wilkins reported on the change in rectus muscles
tile ocular blood flow in the second decade of life and found in childhood and noted there was great variation in size
that there was a significantly higher rate of flow and pulsatile between individual children with the average muscle
amplitude as compared to later decades of life [75]. They 2.5–3 mm narrower than adults [19]. Growth continued
measured the flow to be 819 ± 212 and 654 ± 176 μL/min in throughout the first years of life with adult-like dimensions
the sitting and supine positions respectively between 10 and being reached by 20 months old [19].
20 years with adult values showing on average a much
smaller difference between sitting and supine (age 71–80 sit- Muscle Length
ting 630 ± 194 and supine 560 ± 147). This suggests imma- The four rectus muscle all arise from the annulus of Zinn, at
ture autoregulation in childhood [75]. the apex of the orbit [150]. Their tendon lengths measure
3.0 mm (1.0–7.0), 4.7 mm (3.0–7.0), 7.2 mm (4.0–11.0) and
4.3 mm (2.0–6.0) for the medial, inferior, lateral and superior
Extraocular Muscles rectus muscles respectively. The rectus muscles show promi-
nent growth throughout childhood (Fig. 1.7) [151].
Anatomy
 he Oblique Muscles
T
Tenon Capsule The superior oblique arises superiomedial to the annulus of
As is evident at surgery on infants and children, Tenon cap- Zinn at the frontoethmoidal suture at the orbital apex and
sule is thicker and more abundant. This appears as a sonolu- courses anteriorly where it is redirected at a 54° angle poste-
cent zone around the sclera on B-scan ultrasound of newborns riorly at the trochlea, a 6 mm by 4 mm curved plate of hya-
up to 44 weeks gestation but is particularly evident in low line cartilage affixed to the trochlear fossa of the frontal bone.
birth weight infants and those babies with shorter axial lengths The muscle is divided into the length from its origin to the
[122]. This finding on ultrasonography is consistent with the trochlea which in adulthood is 40 mm and the reflected part
work of Shauly and coworkers who found that Tenon’s cap- from trochlea to insertion which measures 20 mm. The mus-
sule in children has thicker collagen fibrils and a greater mean cle belly becomes tendenous approximately 10 mm prior to
number of collagen fibrils when compared to older age groups the trochlea and fans out at its insertion of variable width of
[147]. They studied children ages 1 month to 12 years old 10–18 mm [63]. The shortest extraocular muscle is the infe-
(mean 5.9 years old) and found a mean collagen fibril diam- rior oblique measuring 37 mm in length with a short tendon
eter of 86 ± 5 nm and mean area of 5299 ± 561 nm2 [147]. measuring between 1 to 2 mm [149, 152]. While adult dimen-
sions are available for the oblique muscles, little work on the
Muscle Width growth of these muscles through childhood is available.
The normal adult muscle measurements have been generated
based on CT scan imaging [146]. Nugent and coworkers Muscle Insertions
measured the width of the horizontal recti on axial and the The rectus muscles insert at various distances behind the lim-
vertical recti on coronal cuts (Table 1.8) [146]. Adult muscle bus in a gradual progression, the spiral of Tillaux, which
diameter measurements along with width of muscle insertion increases from the medial, inferior, lateral and superior rectus.

Table 1.8  CT scan extraocular muscle diameter and width of insertion by age (mm) [19, 146]
Width Width Width Width Width
of insertion of insertion of insertion of insertion of insertion Width Adult
neonatal 2–3 month 6 months 9 months 20 months of insertion diameter ±
(mm) (mm) (mm) (mm) (mm) adult (mm) SD (mm)
Medial rectus muscle 7.6 6.8 9.0 8.7 8.9 10.5 4.1 ± 0.5
Inferior rectus muscle 6.8 6.7 8.3 8.3 9.3 9.8 4.9 ± 0.8
Superior rectus muscle 7.5 7.3 8.9 8.8 10.2 10.8 3.8 ± 0.7a
Lateral rectus muscle 6.9 7.0 8.4 8.2 7.8 9.2 2.9 ± 0.6
Superior oblique muscle N/A N/A N/A N/A N/A N/A 2.4 ± 0.4
Superior Rectus Muscle Group (combined superior rectus/levator palpebrae complex)
a

N/A not available

16 L.J. Heinmiller and A.V. Levin

45 Ocular Alignment
Medial Rectus
Inferior rectus
40 Lateral Rectus Binocularity Development
Superior Rectus Binocularity is not present at birth [154, 155]. It develops in
the first 2–4 months of life only with binocularly coordinated
35
visual stimulation such that the presence of ocular misalign-
ment, media opacities (e.g. cataract), or large uncorrected
30 refractive errors may preclude the proper development of
normal stereopsis [154, 155]. It has been shown using indi-
25 viduals that have experienced esotropia through varying
periods of their lives that several months after birth a sensi-
20 tive period for binocularity begins and peaks between 1–3
years of age [156]. In addition, Molteno and coworkers
extrapolated data gathered by photoscreening to estimate
15
Premature Infant 1 year old 20-30 years old that simultaneous perception develops by 3–4 months, ste-
reoscopic depth perception by 5 months, and the ability to
Fig. 1.7  Length (mm) of rectus muscles with age (mean) [151] converge and accommodate accurately by 6 months [6].

Phorias
Several very large studies have been done in which the ocular
The average adult insertion points behind the limbus are alignment of thousands of babies has been examined. Archer
5.5 mm for the medial rectus, 6.5 mm for the inferior rectus, and coworkers reported that just over 75 % of normal infants
6.9 mm for the lateral rectus and 7.7 mm for superior rectus. of gestational age ≥36 weeks will have a constant or intermit-
In infants, the corneal-limbal distance measures 5.0 mm, tent exotropia in the first 2 months of life [157]. In the first few
6.3 mm, 6.1 mm and 6.5 mm for the medial, inferior, lateral days of life 33–66 % will have either constant or intermittent
and superior rectus respectively [150]. At birth, the rectus exotropia [158, 159] although Chace and coworkers (while
muscles insert approximately 2 mm closer to the limbus than examining the incidence of retinal hemorrhages) noted an
in adults decreasing to 1 mm at age 6–9 months and reaching incidence of only 1.8 % in babies who had been pharmacologi-
adult distances by 20 months old [19, 150]. cally cyclopleged [160]. As the infant ages the frequency and
The superior oblique muscle passes between the superior size of the deviations decrease such that only 10 % of infants
rectus and the globe inserting obliquely with the anterior are exotropic by 4 months of age and none are constantly exo-
insertion in adults 13.8 mm on average from the limbus and tropic by 8 months [157]. There may be great day-to-day vari-
3.0–4.5 mm behind the lateral end of the superior rectus ability in ocular alignment in the first 4 months of life [157].
muscle insertion. The posterior portion inserts 18.8 mm on Sondhi and coworkers found that 2.6 % of babies showed
average from the limbus and 13.6 mm behind the medial end swings between esotropia and exotropia [159]. Esodeviations
of the superior rectus muscle insertion [152]. The width of are very unusual at birth (0.2–1.8 %) and when present are
the insertion varies widely from 7 to 18 mm but averages usually small and intermittent [157–160]. They are rare after
about 11 mm [149, 152]. 2 months of age [159]. However, brief episodes of “conver-
The inferior oblique arises from the orbital plate of the gence spasm” with simultaneous adduction of both eyes, can
maxilla anteriorly and courses below the inferior rectus mus- often be seen in normal children up to 4 months old [159].
cle to insert on the posterio-lateral aspect of the globe. The
anterior margin of the insertion is approximately 10 mm pos-  ormal Deviations of Infancy
N
terior to the inferior edge of the lateral rectus insertion. The Cranial nerve palsies causing strabismus in the neonatal
posterior edge of the inferior oblique insertion is located period are extremely rare. The incidence of sixth cranial
1 mm below and 1–2 mm anterior to the macula. to the lower nerve palsy, which often resolves spontaneously, is less than
edge of the insertion of the lateral rectus with the posterior 0.09 % [159]. Based on this data we would recommend
insertion 3–6 mm anterior to the optic nerve and 1 mm below observation of ocular misalignment in the first 4 months of
and 1–2 mm anterior to the macula [153]. The concavity of life particularly if the deviation is small, intermittent,
the insertion is towards the origin of the muscle and the decreasing in size and frequency over time, and exotropic.
width of the insertion point varies greatly from 5 to 14 mm Exotropic babies showing improvement through the fourth
with an average of 9 mm [153]. month may be observed until 7 or 8 months as long as visual
1  Normal Postnatal Ocular Development 17

acuity appears to be unaffected and the trend for resolution Tonic Downgaze
continues. Esotropic babies should not be referred earlier as Variations in ocular movement may also be normal in
should any baby with a constant large angle strabismus. infants. Tonic downgaze is occasionally seen (<1 %) with or
Children who are premature and those who demonstrate neu- without upper eyelid retraction especially in response to
rologic impairment, visual compromise, abnormalities of sudden dimming of the lights (eye popping reflex) [157].
ocular movement, or signs of other strabismus syndromes Usually, one can determine that this is a normal variant by
may require more aggressive management. brightening the ambient lighting or attracting the infant’s
attention and fixation [157]. Benign paroxysmal tonic down-
gaze may rarely be associated with vertical nystagmus and
Ocular Movement resolves within the first year of life (usually in first 6 months)
with persistence possibly indicating neurological disease
Saccades [172, 173].
Normal neonates are capable of following large objects usu-
ally by making use of head and eye movements. Saccades
develop at a faster rate than smooth pursuit [161]. Garbutt Craniofacial
and coworkers studied saccades in infants ages 2–18 months
old with adult comparison and found from the age of Detailed studies have been conducted regarding the
2 months, the infants were able to generate saccades at growth of the cranial vault, cranial base skull and face. As
speeds similar to or faster than the adult population and these factors influence the eye and orbit only by indirect
showed no statistical difference between peak velocity or means, the reader is referred elsewhere for further details
duration [162]. Metz showed that prism induced shifts in [174, 175].
fixation were equivalent to voluntary shifts in fixation in a
cooperative population (age 10–79 years old) with an infant
population showing good reproducibility [163]. Eyelids

Smooth Pursuit  alpebral Fissure Height and Length

P
Smooth pursuit develops rapidly in the first 3 months of life Palpebral fissure length at 40 weeks gestation is
but has still not reached adult levels of gain by 6 months 1.85 ± 0.13  cm [176]. Duke-Elder reported a progression of
[161]. Asymmetry of smooth pursuit movements are normal palpebral fissure length from 1.99 cm at 1–6 months of age
in these first 6 months although more prominent in the first to 2.84 cm at age 16–18 years old [177]. There have been
3 months [161]. This lack of smooth pursuit has been attrib- studies showing that blacks have the longest palpebral fis-
uted to the lack of foveal maturity [164]. Salman and sures compared to Hispanic and white children [178]. The
coworker studied smooth pursuit in children ages 8–19 years horizontal palpebral fissure length (PFL) may become short-
old and found that smooth pursuit gains increased with age ened on forced lid closure. It has been suggested that the
(P < 0.01), with vertical gains having large variability among amount of shortening should not exceed 4 mm in normal
participants and with horizontal gains reaching adult values children [179]. Abnormal PFL shortening may be due to
by mid adolescence [165]. Table 1.9 illustrates ages of major defective insertion or absence of the lateral canthal tendon
milestones in the visual system [7, 166–171]. [179]. Paiva and coworkers studied palpebral changes in
childhood and noted at birth, the upper eyelid was at its low-
Table 1.9  Maturation of vision [7, 166–171] est position with the lower eyelid margin close to the pupil
Age Description center [180]. After 3 months of age, the distance between
34 weeks gestation Vestibular eye rotations well developed the lower eyelid margin and pupil center increased linearly
Birth Visual fixation present until 18 months when the position stabilized while the upper
Conjugate horizontal gaze well developed eyelid reaches maximum position between ages 3 and
Optokinetic nystagmus well developed 6 months then declines linearly [180]. At birth, a single
1 month Ocular alignment stable crease was the most common lower eyelid pattern with the
2–3 months Fixation well developed proportion of patients showing a double crease increasing
Conjugate vertical gaze well developed with age until 36 months when the double crease pattern
Demonstrate stereopsis becomes the most common [180]. Palpebral fissure length in
3 months Visual following well developed caucasians can be calculated based upon work done by
4 month Accommodation well developed Chouke using the formula PFL = (Outer Canthal
6 months Fusional convergence well developed Distance − Inner Canthal Distance)/2.
18 L.J. Heinmiller and A.V. Levin

Inner Canthal Distance Superior Ophthalmic Vein

Inner canthal distance in the distance measured between the The superior ophthalmic vein in adulthood measures
medial canthi of each eye. Normative values for inner can- 1.8 ± 0.5 mm on axial CT cuts and 2.7 ± 1.0 mm on coronal
thal distance have been established by Feingold and Bossert views [146]. It appears larger and more readily visible on
using direct measurement [181]. These values were obtained B-scan in neonates, particularly premature infants, up to
through study of 2403 newborns to age 14 years old [181]. 46 weeks [122]. This may due to the closer relationship to
the superior rectus in this age group causing partial compres-
sion with secondary dilation [122].
Outer Canthal Distance

Outer canthal distance is the distance measured between the Interorbital Distance
lateral canthi of each eye. Feingold and Bossert adjust the
OCD in girls between 1–4 years old by adding the value of When assessing a child for hypertelorism or hypotelorism,
0.2 cm and normative values can be used for ­comparison [181]. one must measure the interorbital distance (IOD) which is
the distance between the two anterior medial orbital walls
measured radiographically. Morin and coworkers showed
Orbit that IOD increases approximately 10 mm from birth to adult-
hood based on examinations of 600 cephalometrograms
Measurements (Fig. 1.8) [15]. Fifty percent of this growth occurs in the first
3 years of life followed by a slower rate of growth, approxi-
At birth, the orbital cavity is 75 % of adult size and continues mately 0.5 mm per year, until 12 years of age after which the
to grow passively in response to globe growth before reach- growth slows but continues until adulthood [15]. They also
ing adult size by age 7 years old [182]. The volume of the noted that even though the range of variation in IOD around
orbit at birth is 10.3 mm3, doubling by age 1 year old to the mean was 9.0 mm at all ages, each child followed its own
22.3 mm3, enlarging further to 39.1 mm3 by age 6–8 years IOD growth curve such that reasonable predictions about
old and measuring 52.4 and 59.2 mm3 for the adult female eventual outcome could be made [15]. Hellman found values
and male respectively [63]. The orbital roof in infants is flat- similar to Morin’s based on measurements taken from a
ter and larger than in adults with the greater wing of the sphe- small series of native American Indian skulls measuring
noid contributing more significantly to the lateral orbital wall interorbital distance at the dacryon (juncture of frontal and
[63]. The changes in orbital opening with age can be found in lacrimal bones): early infancy mean 15.89 ± 1.10, late infancy
Table 1.10 [183, 184]. The optic canal and bony orbit reach mean 17.67 ± 0.94, childhood mean 18.0 ± 1.53, and puberty
adult levels by age 10 years with the infant optic canal mea- 21.40 ± 1.20 [175].
suring 3.5 mm in diameter reaching adult diameter of 5.5 mm
by 5 years old [182]. Nugent and coworkers determined the
normal adult position of the globe by measuring the distance Interpupillary Distance
between the most posterior aspect of the sclera relative to a
horizontal line joining the two zygoma (interzygomatic line) Interpupillary distance (IPD), although difficult to measures
[146]. The normal position was 9.9 ± 1.7 mm posterior to this due to errors induced by accommodative convergence, has
line [146]. The main structures affecting the change in inter- been studied in normal individuals. IPD can also be calcu-
orbital dimensions are the ethmoid aircells [15]. lated using the Feingold and Bossert method formula:
IPD = 0.7 + (0.59 × ICD) + (0.41 × OCD) [181]. The rate of
change in IPD can be calculated using the linear regression
Table 1.10  Changes in orbital opening by age [183, 184] formula y = 0.78x + 47.48 where y is the IPD and x the age
Age Height (mm) Width (mm) [185]. However, the rate of change in females and in children
Newborn (6 months) 27 27 below 5 years old are both significantly higher than males
Child (7 years) 28 33 and children over 5 respectively [185]. The authors offer for-
Adult Males: 32.44 ± 1.89 Males: 37.42 ± 2.44 mulas for each subgroup [185]. The Mustardé Index defines
Females: 31.75 ± 2.44 Females: 36.60 ± 1.71 the normal ratio of ICD/IPD as ≤0.55 [186].
1  Normal Postnatal Ocular Development 19

Mean Interorbital Distance (mm) by Age (years) Table 1.11  Development of paranasal sinuses by age [187, 188]
25 Frontal Sphenoid Maxillary Ethmoid
23 Newborn
Length (mm) – – 10 10
21 Width (mm) – – 3 2
19 Height (mm) – – 4 2.5
1–4 year old
17 Length 6 5 26 15.5
15 Width 5.5 7 15 8
Height 7.5 4 15 12
13 4–8 year old
0.3 1.5 3 5 7 9 11 > 20
Length 8 12.5 36 21
Fig. 1.8  Mean interorbital distance (mm) by age (years) [15] Width 9 10 21 11
Height 15.5 9 24 12.5
16 year old
Length (mm) 12.8 ± 5.0 23.0 ± 4.5 38.8 ± 3.5
Width (mm) 21.9 ± 8.4 12.8 ± 3.1 27.5 ± 4.2
Sinuses Height (mm) 24.5 ± 13.3 22.6 ± 5.8 36.3 ± 6.2

Rate of Growth
Tomonaga used Goldmann perimetry in 4–10 year olds and
At birth, the ethmoidal air cells occupy most of the medial found the adult size of visual field was reached by age 5 [191].
orbital wall [15]. By 7 years of age the ethmoid air cells rep- Conversly, Lakowski and Aspinall used Goldmann static
resent only half of the medial wall as the maxillary air cells perimetry found a constricted visual field to 15° at age 5–6
have grown in the interim [15]. The frontal sinus is not pres- years old and adult size visual fields by age 12 years old [192].
ent at birth and later develops from the anterior ethmoidal
cells beginning at 6–12 months of age [15]. Thereafter, the
frontal sinuses expand superolaterally rapidly until the third References
year of life after which slow growth continues well into
adulthood [15]. The sphenoid sinus, present at birth, also 1. Wilmer HA, Scammon RE. Growth of the components of the
continues growth until approximately 3 years old [15]. A human eyeball. I. Diagrams, calculations, computation and refer-
ence tables. Arch Ophthalmol. 1950;43:599–619.
rudimentary maxillary sinus is present at birth although the 2. Ciancia AO. Management of esodeviations under the age of two.
superior alveolar ridge lies in close proximity to the orbital Int Ophthalmol Clin. 1966;6:503–18.
floor [15]. The majority of maxillary sinus growth occurs 3. Pieh C, Proudlock F, Gottlob I. Smooth pursuit in infants: maturation
between 3–4 years after which slow growth continues until and the influence of stimulation. Br J Ophthalmol. 2012;96:73–7.
4. Goren CC, Sarty M, Wu PY. Visual following and pattern discrim-
15 years [15]. Table 1.11 illustrates the development of each ination of face-like stimuli by newborn infants. Pediatrics.
sinus by age group [187, 188]. 1975;56:544–9.
5. Fitzgerald HE. Autonomic pupillary reflex activity during early
infancy and its relation to social and nonsocial visual stimuli.
J Exp Child Psychol. 1968;6:470–82.
Visual Fields 6. Molteno AC, Hodgkinson IJ, Hewitt CJ, Sanderson GF. The devel-
opment of fixing and focusing behaviour in normal human infants
Normative Values as observed with the Otago photoscreener. Aust N Z J Ophthalmol.
1992;20:197–205.
7. Dobson V, Teller DY. Visual acuity in human infants: a review and
Attempts have been made to establish normal standards for comparison of behavioral and electrophysiological studies. Vision
visual fields in children with variable success. Wilson and Res. 1978;18:1469–83.
coworkers found a growth in the size of the visual field 8. Lewis TL, Maurer D, Brent HP. Development of grating acuity in
between the ages of 4 and 12 years [189]. Based on this data, children treated for unilateral or bilateral congenital cataract.
Invest Ophthalmol Vis Sci. 1995;36:2080–95.
by 11.6 years old the adult visual field size is obtained [189]. 9. Norcia AM, Tyler CW. Spatial frequency sweep VEP: visual acu-
They established normative values in this age range although ity during the first year of life. Vision Res. 1985;25:1399–408.
the accuracy of their values has been questioned based upon 10. Allen D, Tyler CW, Norcia AM. Development of grating acuity
the difficulty of standardizing responses in children under and contrast sensitivity in the central and peripheral visual field of
the human infant. Vision Res. 1996;36:1945–53.
5 years old particularly using the double arc perimeter 11. McMillan JA, Oski FAP. Practice of p. Oski’s pediatrics: princi-
method [190]. Other studies have been variable in the ples & practice. 4th ed. Philadelphia, PA/London: Lippincott
reported progression of visual fields throughout childhood. Williams & Wilkins; 2006.
20 L.J. Heinmiller and A.V. Levin

12. Banks MS, Salapatek P. Acuity and contrast sensitivity in 1-, 2-, 36. Wallman J. Nature and nurture of myopia. Nature. 1994;371:201–2.
and 3-month-old human infants. Invest Ophthalmol Vis Sci. 37. Valluri S, Minkovitz JB, Budak K, et al. Comparative corneal
1978;17:361–5. topography and refractive variables in monozygotic and dizygotic
13. Fiorentini A, Pirchio M, Spinelli D. Scotopic contrast sensitivity twins. Am J Ophthalmol. 1999;127:158–63.
in infants evaluated by evoked potentials. Invest Ophthalmol Vis 38. Zadnik K, Satariano WA, Mutti DO, Sholtz RI, Adams AJ. The
Sci. 1980;19:950–5. effect of parental history of myopia on children’s eye size. JAMA.
14. Kushner BJ, Lucchese NJ, Morton GV. Variation in axial length 1994;271:1323–7.
and anatomical landmarks in strabismic patients. Ophthalmology. 39. McKean-Cowdin R, Varma R, Cotter SA, et al. Risk factors for
1991;98:400–6. astigmatism in preschool children: the multi-ethnic pediatric eye
15. Morin JD, Hill JC, Anderson JE, Grainger RM. A study of growth disease and Baltimore pediatric eye disease studies.
in the interorbital region. Am J Ophthalmol. 1963;56:895–901. Ophthalmology. 2011;118:1974–81.
16. Fledelius HC, Christensen AC. Reappraisal of the human ocular 40. Isenberg SJ, Apt L, McCarty J, Cooper LL, Lim L, Del Signore
growth curve in fetal life, infancy, and early childhood. Br M. Development of tearing in preterm and term neonates. Arch
J Ophthalmol. 1996;80:918–21. Ophthalmol. 1998;116:773–6.
17. Stafford Jr JR, Rosen TS, Zaider M, Merriam JC. Prenatal cocaine 41. Toker E, Yenice O, Ogut MS, Akman I, Ozek E. Tear production
exposure and the development of the human eye. Ophthalmology. during the neonatal period. Am J Ophthalmol. 2002;133:746–9.
1994;101:301–8. 42. Katowitz JA. Pediatric oculoplastic surgery. New York/London:
18. Larsen JS. The sagittal growth of the eye. IV. Ultrasonic measure- Springer; 2002.
ment of the axial length of the eye from birth to puberty. Acta 43. Della Rocca RC, Bedrossian EH, Arthurs BP. Ophthalmic plastic
Ophthalmol (Copenh). 1971;49:873–86. surgery: decision making and techniques. New York/London:
19. Swan KC, Wilkins JH. Extraocular muscle surgery in early McGraw-Hill, Medical Publishing Division; 2002.
infancy—anatomical factors. J Pediatr Ophthalmol Strabismus. 44. Cohen AJ, Brazzo BG, Mercandetti M. The lacrimal system: diag-
1984;21:44–9. nosis, management, and surgery. New York: Springer; 2006.
20. Ellis F. Surgical choices: how does the infant eye differ from the 45. Guerry 3rd D, Kendig Jr EL. Congenital impatency of the nasolac-
adult’s: the role of the intraocular lens. Am Orthop J. 1997;47:12–6. rimal duct. Arch Ophthalmol. 1948;39:193–204.
21. Hahn FJ, Chu WK. Ocular volume measured by CT scans. 46. Cassady JV. Developmental anatomy of nasolacrimal duct. AMA
Neuroradiology. 1984;26:419–20. Arch Ophthalmol. 1952;47:141–58.
22. Abrahamsson M, Fabian G, Andersson AK, Sjostrand J. A longi- 47. Speedwell L, Novakovic P, Sherrard ES, Taylor DS. The infant
tudinal study of a population based sample of astigmatic children. corneal endothelium. Arch Ophthalmol. 1988;106:771–5.
I. Refraction and amblyopia. Acta Ophthalmol (Copenh). 48. Isenberg SJ, Del Signore M, Chen A, Wei J, Christenson
1990;68:428–34. PD. Corneal topography of neonates and infants. Arch Ophthalmol.
23. Aurell E, Norrsell K. A longitudinal study of children with a fam- 2004;122:1767–71.
ily history of strabismus: factors determining the incidence of 49. Snir M, Axer-Siegel R, Bourla D, Kremer I, Benjamini Y,
strabismus. Br J Ophthalmol. 1990;74:589–94. Weinberger D. Tactile corneal reflex development in full-term
24. Kuo A, Sinatra RB, Donahue SP. Distribution of refractive error in babies. Ophthalmology. 2002;109:526–9.
healthy infants. J AAPOS. 2003;7:174–7. 50. Portellinha W, Belfort Jr R. Central and peripheral corneal thick-
25. Ehrlich DL, Atkinson J, Braddick O, Bobier W, Durden ness in newborns. Acta Ophthalmol (Copenh). 1991;69:247–50.
K. Reduction of infant myopia: a longitudinal cycloplegic study. 51. Remon L, Cristobal JA, Castillo J, Palomar T, Palomar A, Perez
Vision Res. 1995;35:1313–24. J. Central and peripheral corneal thickness in full-term newborns
26. Harley RD, Nelson LB, Olitsky SE. In: Nelson LB, Olitsky SE, by ultrasonic pachymetry. Invest Ophthalmol Vis Sci.
editors. Harley’s pediatric ophthalmology. 5th ed. Philadelphia: 1992;33:3080–3.
Lippincott Williams & Wilkins; 2005. 52. Lopez JP, Freedman SF, Muir K, et al. Central corneal thickness in
27. Brown NP, Koretz JF, Bron AJ. The development and maintenance children and adolescents with pediatric glaucoma and eye disor-
of emmetropia. Eye (Lond). 1999;13(Pt 1):83–92. ders at risk of developing glaucoma. J Pediatr Ophthalmol
28. Fulton AB, Dobson V, Salem D, Mar C, Petersen RA, Hansen Strabismus. 2010;48(2):108–16.
RM. Cycloplegic refractions in infants and young children. Am 53. Ehlers N, Sorensen T, Bramsen T, Poulsen EH. Central corneal
J Ophthalmol. 1980;90:239–47. thickness in newborns and children. Acta Ophthalmol (Copenh).
29. Mayer DL, Hansen RM, Moore BD, Kim S, Fulton AB. Cycloplegic 1976;54:285–90.
refractions in healthy children aged 1 through 48 months. Arch 54. Dimasi DP, Burdon KP, Craig JE. The genetics of central corneal
Ophthalmol. 2001;119:1625–8. thickness. Br J Ophthalmol. 2010;94:971–6.
30. Deng L, Gwiazda JE. Anisometropia in children from infancy to 55. Lim L, Gazzard G, Chan YH, et al. Corneal biomechanics, thick-
15 years. Invest Ophthalmol Vis Sci. 2012;53(7):3782–7. ness and optic disc morphology in children with optic disc tilt. Br
31. Inagaki Y. The rapid change of corneal curvature in the neonatal J Ophthalmol. 2008;92:1461–6.
period and infancy. Arch Ophthalmol. 1986;104:1026–7. 56. Kirwan C, O’Keefe M, Lanigan B. Corneal hysteresis and intra-
32. Ingram RM, Walker C, Wilson JM, Arnold PE, Dally S. Prediction ocular pressure measurement in children using the reichert ocular
of amblyopia and squint by means of refraction at age 1 year. Br response analyzer. Am J Ophthalmol. 2006;142:990–2.
J Ophthalmol. 1986;70:12–5. 57. Kirwan C, O’Keefe M. Corneal hysteresis using the Reichert ocu-
33. Borchert MS, Varma R, Cotter SA, et al. Risk factors for hypero- lar response analyser: findings pre- and post-LASIK and
pia and myopia in preschool children the multi-ethnic pediatric LASEK. Acta Ophthalmol. 2008;86:215–18.
eye disease and Baltimore pediatric eye disease studies. 58. Ortiz D, Pinero D, Shabayek MH, Arnalich-Montiel F, Alio
Ophthalmology. 2011;118:1966–73. JL. Corneal biomechanical properties in normal, post-laser in situ
34. Rosenbloom AA, Morgan MW. Principles and practice of pediat- keratomileusis, and keratoconic eyes. J Cataract Refract Surg.
ric optometry. Philadelphia, PA: Lippincott; 1990. 2007;33:1371–5.
35. Zadnik K, Mutti DO, Friedman NE, Adams AJ. Initial cross-­ 59. Lim L, Cheung N, Gazzard G, Chan YH, Wong TY, Saw
sectional results from the Orinda longitudinal study of myopia. SM. Corneal biomechanical properties and retinal vascular caliber
Optom Vis Sci. 1993;70:750–8. in children. Invest Ophthalmol Vis Sci. 2009;50:121–5.
1  Normal Postnatal Ocular Development 21

60. Kiryu J, Park M, Kobayashi H, Kondo T. Ultrasound biomicros- 86. Isenberg SJ, Dang Y, Jotterand V. The pupils of term and preterm
copy of the anterior segment of the eyes of infants. J Pediatr infants. Am J Ophthalmol. 1989;108:75–9.
Ophthalmol Strabismus. 1998;35:320–2. 87. Taylor D. Pediatric ophthalmology. Boston: Blackwell Scientific;
61. Tawara A, Inomata H, Tsukamoto S. Ciliary body band width as 1990.
an indicator of goniodysgenesis. Am J Ophthalmol. 1996;122: 88. Ansons AM, Davis H, Mein JD. Diagnosis and management of
790–800. ocular motility disorders. 3rd ed. Oxford: Blackwell Science; 2001.
62. Shields MB. Textbook of glaucoma. 2nd ed. Baltimore/London: 89. Stidwill D. Orthoptic assessment and management. 2nd ed.
Williams & Wilkins; 1987. Oxford: Blackwell Scientific; 1998.
63. Wright KW, Spiegel PH. Pediatric ophthalmology and strabismus. 90. Spierer A, Isenberg SJ, Inkelis SH. Characteristics of the iris in
In: Wright KW, Spiegel PH, Hengst TC, Gilbert S, Cogswell F, 100 neonates. J Pediatr Ophthalmol Strabismus. 1989;26:28–30.
editors. Illustrators. 2nd ed. New York/London: Springer; 2003. 91. Bito LZ, Matheny A, Cruickshanks KJ, Nondahl DM, Carino
64. Chandler PA, Grant WM. Glaucoma. 2nd ed. Philadelphia: Lea & OB. Eye color changes past early childhood. The Louisville Twin
Febiger; 1979. Study. Arch Ophthalmol. 1997;115:659–63.
65. Crawford JS, Morin JD. The Eye in childhood. New York/London: 92. Bluestein EC, Wilson ME, Wang XH, Rust PF, Apple
Grune & Stratton; 1983. DJ. Dimensions of the pediatric crystalline lens: implications for
66. Walton DS. Primary congenital open angle glaucoma: a study of intraocular lenses in children. J Pediatr Ophthalmol Strabismus.
the anterior segment abnormalities. Trans Am Ophthalmol Soc. 1996;33:18–20.
1979;77:746–68. 93. Dub B. Beltrag Zur Kenntniss der Cataracta Zonularis. Graef Arch
67. Giles CL. Tonometer tensions in the newborn. AMA Arch 1891;4.
Ophthalmol. 1959;61:517–19. 94. Sakabe I, Oshika T, Lim SJ, Apple DJ. Anterior shift of zonular
68. Radtke ND, Cohan BE. Intraocular pressure measurement in the insertion onto the anterior surface of human crystalline lens with
newborn. Am J Ophthalmol. 1974;78:501–4. age. Ophthalmology. 1998;105:295–9.
69. Dolcet L. Ocular tension in the newborn. Archivos Soc Oftalmol 95. Scammon RE, Wilmer HA. Growth of the components of the
Hisp Am. 1952;12:1057–63. human eyeball. II. Comparison of the calculated volumes of the
70. Horven I. Tonometry in newborn infants. Acta Ophthalmol eyes of the newborn and of adults, and their components. Arch
(Copenh). 1961;39:911–18. Ophthalmol. 1950;43:620–37.
71. Kornblueth W, Abrahamov A, Aladjemoff L, Magora F, Gombos 96. Cotlier E, Lambert S, Taylor D. Congenital cataracts. Austin, Tex:
G. Intraocular pressure in the newborn measured under general R. G. Landes; 1994.
anesthesia. Arch Ophthalmol. 1962;67:750–2. 97. Wilson ME, Trivedi RH, Pandey SK. Pediatric cataract surgery:
72. Westby RK, Skulberg A. Tonometry during general anaesthesia. techniques, complications, and management. Philadelphia, Pa/
Acta Ophthalmol (Copenh). 1962;40:186–91. London: Lippincott Williams & Wilkins; 2005.
73. Hetherington Jr J, Shaffer RN. Tonometry and tonography in con- 98. Richburg FA, Sun HS. Size of the crushed cataractous capsule
genital glaucoma. Invest Ophthalmol. 1968;7:134–7. bag. J Am Intraocul Implant Soc. 1983;9:333–5.
74. Sampaolesi R. Ocular pressure and the anterior chamber angle in 99. Fisher RF, Pettet BE. The postnatal growth of the capsule of the
the normal infant and in congenital glaucoma up to 5 years of age. human crystalline lens. J Anat. 1972;112:207–14.
Doc Ophthalmol. 1969;26:497–515. 100. Wilson Jr ME. Anterior lens capsule management in pediatric
75. Ravalico G, Toffoli G, Pastori G, Croce M, Calderini S. Age-­ cataract surgery. Trans Am Ophthalmol Soc. 2004;102:391–422.
related ocular blood flow changes. Invest Ophthalmol Vis Sci. 101. Krag S, Olsen T, Andreassen TT. Biomechanical characteristics of
1996;37:2645–50. the human anterior lens capsule in relation to age. Invest
76. Pensiero S, Da Pozzo S, Perissutti P, Cavallini GM, Guerra Ophthalmol Vis Sci. 1997;38:357–63.
R. Normal intraocular pressure in children. J Pediatr Ophthalmol 102. Khurana AK. Comprehensive ophthalmology. Anshan: Tunbridge
Strabismus. 1992;29:79–84. Wells; 2008 [Rev and updated ed.].
77. Youn DH, Yu YS, Park IW. Intraocular pressure and axial length in 103. Bock P. The distribution of disulfide-groups in Descemet’s mem-
children. Korean J Ophthalmol. 1990;4:26–9. brane, lens capsule, and zonular fibers. Acta Histochem.
78. Jaafar MS, Kazi GA. Normal intraocular pressure in children: a 1978;63:127–36.
comparative study of the Perkins applanation tonometer and the 104. Streeten BW, editor. Anatomy of the zonular apparatus.
pneumatonometer. J Pediatr Ophthalmol Strabismus. Philadelphia: Lippincott-Raven; 1992.
1993;30:284–7. 105. Godfrey M, Nejezchleb PA, Schaefer GB, Minion DJ, Wang Y,
79. Sihota R, Tuli D, Dada T, Gupta V, Sachdeva MM. Distribution Baxter BT. Elastin and fibrillin mRNA and protein levels in the
and determinants of intraocular pressure in a normal pediatric ontogeny of normal human aorta. Connect Tissue Res.
population. J Pediatr Ophthalmol Strabismus. 2006;43:14–8. quiz 1993;29:61–9.
36-17. 106. Kwitko ML. Surgery of the infant eye. New York/London:
80. Eisenberg DL, Sherman BG, McKeown CA, Schuman Appleton-Century-Crofts/Prentice-Hall; 1979.
JS. Tonometry in adults and children. A manometric evaluation of 107. Aiello AL, Tran VT, Rao NA. Postnatal development of the ciliary
pneumatonometry, applanation, and TonoPen in vitro and in vivo. body and pars plana. A morphometric study in childhood. Arch
Ophthalmology. 1998;105:1173–81. Ophthalmol. 1992;110:802–5.
81. Johnson GJ, Corey PN, Morin JD. Tonography in infants and chil- 108. Hartnett ME. Pediatric retina. Philadelphia, PA/London:
dren. Can J Ophthalmol. 1971;6:24–9. Lippincott Williams & Wilkins; 2005.
82. Lundvall A, Svedberg H, Chen E. Application of the ICare 109. Provis JM, van Driel D. Retinal development in humans: the roles
rebound tonometer in healthy infants. J Glaucoma. 2011;20:7–9. of differential growth rates, cell migration and naturally occurring
83. Bordon AF, Katsumi O, Hirose T. Tonometry in pediatric patients: cell death. Aust N Z J Ophthalmol. 1985;13:125–33.
a comparative study among Tono-pen, Perkins, and Schiotz 110. Abramov I, Gordon J, Hendrickson A, Hainline L, Dobson V,
tonometers. J Pediatr Ophthalmol Strabismus. 1995;32:373–7. LaBossiere E. The retina of the newborn human infant. Science.
84. Roarty JD, Keltner JL. Normal pupil size and anisocoria in new- 1982;217:265–7.
born infants. Arch Ophthalmol. 1990;108:94–5. 111. Hendrickson A, Drucker D. The development of parafoveal and
85. Romano PE. Pupillary size in infants. Pediatrics. 1977;60:762. mid-peripheral human retina. Behav Brain Res. 1992;49:21–31.
22 L.J. Heinmiller and A.V. Levin

112. Yuodelis C, Hendrickson A. A qualitative and quantitative analy- 137. Jonas JB, Gusek GC, Naumann GO. Optic disc, cup and neuroreti-
sis of the human fovea during development. Vision Res. nal rim size, configuration and correlations in normal eyes. Invest
1986;26:847–55. Ophthalmol Vis Sci. 1988;29:1151–8.
113. Isenberg SJ. Macular development in the premature infant. Am 138. Sylvester PE, Ari K. The size and growth of the human optic
J Ophthalmol. 1986;101:74–80. nerve. J Neurol Neurosurg Psychiatry. 1961;24:45–9.
114. El-Dairi MA, Asrani SG, Enyedi LB, Freedman SF. Optical coher- 139. Kandasamy Y, Smith R, Wright IM, Hartley L. Optic disc mea-
ence tomography in the eyes of normal children. Arch Ophthalmol. surements in full term infants. Br J Ophthalmol. 2012;96:662–4.
2009;127:50–8. 140. Samarawickrama C, Pai A, Tariq Y, Healey PR, Wong TY,

115. Huynh SC, Wang XY, Rochtchina E, Mitchell P. Distribution of Mitchell P. Characteristics and appearance of the normal optic
macular thickness by optical coherence tomography: findings nerve head in 6-year-old children. Br J Ophthalmol. 2012;96:
from a population-based study of 6-year-old children. Invest 68–72.
Ophthalmol Vis Sci. 2006;47:2351–7. 141. Elia N, Pueyo V, Altemir I, Oros D, Pablo LE. Normal reference
116. Huynh SC, Wang XY, Burlutsky G, Rochtchina E, Stapleton F, ranges of optical coherence tomography parameters in childhood.
Mitchell P. Retinal and optic disc findings in adolescence: a Br J Ophthalmol. 2012;96:665–70.
population-­ based OCT study. Invest Ophthalmol Vis Sci. 142. Richardson KT. Optic cup symmetry in normal newborn infants.
2008;49:4328–35. Invest Ophthalmol. 1968;7:137–40.
117. Stone J, Itin A, Alon T, et al. Development of retinal vasculature is 143. Salchow DJ, Oleynikov YS, Chiang MF, et al. Retinal nerve fiber
mediated by hypoxia-induced vascular endothelial growth factor layer thickness in normal children measured with optical coher-
(VEGF) expression by neuroglia. J Neurosci. 1995;15:4738–47. ence tomography. Ophthalmology. 2006;113:786–91.
118. Birch DG, Anderson JL. Standardized full-field electroretinogra- 144. Wollstein G, Schuman JS. Normative optical coherence tomogra-
phy. Normal values and their variation with age. Arch Ophthalmol. phy measurements in children. Br J Ophthalmol. 2012;96:915–16.
1992;110:1571–6. 145. Ballantyne J, Hollman AS, Hamilton R, et al. Transorbital optic
119. Rodriguez-Saez E, Otero-Costas J, Moreno-Montanes J, Relova nerve sheath ultrasonography in normal children. Clin Radiol.
JL. Electroretinographic changes during childhood and adoles- 1999;54:740–2.
cence. Eur J Ophthalmol. 1993;3:6–12. 146. Nugent RA, Belkin RI, Neigel JM, et al. Graves orbitopathy:
120. Westall CA, Panton CM, Levin AV. Time courses for maturation correlation of CT and clinical findings. Radiology. 1990;177:
­
of electroretinogram responses from infancy to adulthood. Doc 675–82.
Ophthalmol. 1998;96:355–79. 147. Shauly Y, Miller B, Lichtig C, Modan M, Meyer E. Tenon’s cap-
121. Jones HE. Hyaloid remnants in the eyes of premature babies. Br sule: ultrastructure of collagen fibrils in normals and infantile eso-
J Ophthalmol. 1963;47:39–44. tropia. Invest Ophthalmol Vis Sci. 1992;33:651–6.
122. Isenberg SJ, Fishman M. B-scan ocular ultrasonography in pre- 148. Holt JE, O’Connor PS, Douglas JP, Byrne B. Extraocular muscle
term and term infants. J Pediatr Ophthalmol Strabismus. size comparison using standardized A-scan echography and com-
1996;33:314–18. puterized tomography scan measurements. Ophthalmology.
123. Brown GC, Tasman WS. Congenital anomalies of the optic disc. 1985;92:1351–5.
New York/London: Grune & Stratton; 1983. 149. Von Noorden GK, Campos EC. Binocular vision and ocular motil-
124. Delaney Jr WV. Prepapillary hemorrhage and persistent hyaloid ity: theory and management of strabismus. 6th ed. St. Louis, MO:
artery. Am J Ophthalmol. 1980;90:419–21. Mosby; 2002.
125. Sekuler R, Kline D, Dismukes K. Aging and human visual func- 150. Wright KW. Color atlas of ophthalmic surgery: strabismus.
tion. New York: Liss; 1982. Philadelphia: Lippincott; 1991.
126. Hogan MJ. The vitreous, its structure, and relation to the ciliary 151. Mhlendyck H. Wachstum und Lange der ausseren augenmuskeln.
body and retina. Proctor award lecture. Invest Ophthalmol. Ber Zusammenkunft Dtsch Ophthalmol Ges. 1978;75:449–52.
1963;2:418–45. 152. Duke-Elder S, Wybar KC. The anatomy of the visual system. St.
127. Gloor BP, Daicker BC. Pathology of the vitreo-retinal border Louis: Mosby; 1961.
structures. Trans Ophthalmol Soc U K. 1975;95:387–90. 153. Fink WH. Surgery of the vertical muscles of the eye. 2nd ed.
128. Foos RY. Vitreoretinal juncture; topographical variations. Invest Springfield, Ill: Thomas; 1962.
Ophthalmol. 1972;11:801–8. 154. Gregg FM, Parks MM. Stereopsis after congenital monocular
129. McCulloch C. The zonule of Zinn: its origin, course, and inser- cataract extraction. Am J Ophthalmol. 1992;114:314–17.
tion, and its relation to neighboring structures. Trans Am 155. Wright KW, Matsumoto E, Edelman PM. Binocular fusion and
Ophthalmol Soc. 1954;52:525–85. stereopsis associated with early surgery for monocular congenital
130. Sebag J. Anatomy and pathology of the vitreo-retinal interface. cataracts. Arch Ophthalmol. 1992;110:1607–9.
Eye (Lond). 1992;6(Pt 6):541–52. 156. Banks MS, Aslin RN, Letson RD. Sensitive period for the devel-
131. Arciniegas A, Amaya LE. Mechanical behavior of the sclera. opment of human binocular vision. Science. 1975;190:675–7.
Ophthalmologica. 1986;193:45–55. 157. Archer SM, Sondhi N, Helveston EM. Strabismus in infancy.
132. Girard LJ, Neely W, Sampson WG. The use of alpha chymotryp- Ophthalmology. 1989;96:133–7.
sin in infants and children. Am J Ophthalmol. 1962;54:95–101. 158. Nixon RB, Helveston EM, Miller K, Archer SM, Ellis FD.
133. Rakic P, Riley KP. Overproduction and elimination of retinal Incidence of strabismus in neonates. Am J Ophthalmol. 1985;100:
axons in the fetal rhesus monkey. Science. 1983;219:1441–4. 798–801.
134. Hellstrom A, Hard AL, Chen Y, Niklasson A, Albertsson-Wikland 159. Sondhi N, Archer SM, Helveston EM. Development of normal ocu-
K. Ocular fundus morphology in preterm children. Influence of lar alignment. J Pediatr Ophthalmol Strabismus. 1988;25:210–11.
gestational age, birth size, perinatal morbidity, and postnatal 160. Chace RR, Merritt KK, Bellows M. Ocular findings in the new-
growth. Invest Ophthalmol Vis Sci. 1997;38:1184–92. born infant; a preliminary report. Arch Ophthalmol. 1950;44:
135. Mansour AM. Racial variation of optic disc parameters in chil- 236–42.
dren. Ophthalmic Surg. 1992;23:469–71. 161. Jacobs M, Harris CM, Shawkat F, Taylor D. Smooth pursuit devel-
136. Rimmer S, Keating C, Chou T, et al. Growth of the human optic opment in infants. Aust N Z J Ophthalmol. 1997;25:199–206.
disk and nerve during gestation, childhood, and early adulthood. 162. Garbutt S, Harwood MR, Harris CM. Infant saccades are not slow.
Am J Ophthalmol. 1993;116:748–53. Dev Med Child Neurol. 2006;48:662–7.
1  Normal Postnatal Ocular Development 23

163. Metz HS. Calibration of saccades in infants. Invest Ophthalmol 180. Paiva RS, Minare-Filho AM, Cruz AA. Palpebral fissures changes
Vis Sci. 1984;25:1233–4. in early childhood. J Pediatr Ophthalmol Strabismus. 2001;38:
164. Kremenitzer JP, Vaughan Jr HG, Kurtzberg D, Dowling 219–23.
K. Smooth-pursuit eye movements in the newborn infant. Child 181. Feingold M, Bossert WH. Normal values for selected physical
Dev. 1979;50:442–8. parameters: an aid to syndrome delineation. Birth Defects Orig
165. Salman MS, Sharpe JA, Lillakas L, Dennis M, Steinbach Artic Ser. 1974;10:1–16.
MJ. Smooth pursuit eye movements in children. Exp Brain Res. 182. Kirks DR, Griscom NT. Practical pediatric imaging: diagnostic
2006;169:139–43. radiology of infants and children. 3rd ed. Philadelphia: Lippincott-­
166. Nelson LB, editor. The pediatric clinics of North America. Raven; 1998.
Philadelphia: W. B. Saunders Company; 1983. 183. Bron AJ, Tripathi RC, Tripathi BJ, Wolff EA. Wolff’s anatomy of
167. Taylor D, Hoyt CS. Pediatric ophthalmology and strabismus. 3rd the eye and orbit. 8th ed. London: Chapman & Hall Medical;
ed. London/New York: Elsevier Saunders; 2005. 1997.
168. Donat JF, Donat JR, Lay KS. Changing response to caloric stimu- 184. Weaver AA, Loftis KL, Tan JC, Duma SM, Stitzel JD. CT based
lation with gestational age in infants. Neurology. 1980;30:776–8. three-dimensional measurement of orbit and eye anthropometry.
169. Hoyt CS, Nickel BL, Billson FA. Ophthalmological examination of the Invest Ophthalmol Vis Sci. 2010;51:4892–7.
infant. Developmental aspects. Surv Ophthalmol. 1982;26:177–89. 185. Chen AH, O’Leary DJ. Changes in the interpupillary distance
170. Banks MS. Infant refraction and accommodation. Int Ophthalmol with age and its effect on the near fusion free position. Aust N Z
Clin. 1980;20:205–32. J Ophthalmol. 1997;25 Suppl 1:S6–8.
171. Liebman SD, Gellis SS. The pediatrician’s ophthalmology; a col- 186. Mustarde J. Epicanthal folds and the problem of telecanthus.
laborative effort of several authors. Saint Louis: Mosby; 1966. Trans Ophthalmol Soc U K. 1963;83:397–411.
172. Allen NM, Tibussek D, Borusiak P, King MD. Images in neonatal 187. Wolf G, Anderhuber W, Kuhn F. Development of the paranasal
medicine. Benign tonic downgaze of infancy. Arch Dis Child sinuses in children: implications for paranasal sinus surgery. Ann
Fetal Neonatal Ed. 2010;95:F372. Otol Rhinol Laryngol. 1993;102:705–11.
173. Hoyt CS, Mousel DK, Weber AA. Transient supranuclear distur- 188. Barghouth G, Prior JO, Lepori D, Duvoisin B, Schnyder P,
bances of gaze in healthy neonates. Am J Ophthalmol. 1980;89: Gudinchet F. Paranasal sinuses in children: size evaluation of
708–13. maxillary, sphenoid, and frontal sinuses by magnetic resonance
174. Ford E. Growth of the human cranial base. Am J Orthod. 1958;44: imaging and proposal of volume index percentile curves. Eur
498–506. Radiol. 2002;12:1451–8.
175. Hellman M. Changes in the human face brought about by develop- 189. Wilson M, Quinn G, Dobson V, Breton M. Normative values
ment. Int J Orthodontics. 1927;13:475–516. for visual fields in 4- to 12-year-old children using kinetic
176. Jones KL, Hanson JW, Smith DW. Palpebral fissure size in new- perimetry. J Pediatr Ophthalmol Strabismus. 1991;28:151–3.
born infants. J Pediatr. 1978;92:787. ­discussion 154.
177. Duke-Elder SS, Perkins ESS. System of ophthalmology. St. Louis: 190. Buncic JR. Normative values for visual fields in 4- to 12- year-old
Mosby; 1966. children using kinetic perimetry:discussion. J Pediatr Ophthalmol
178. Iosub S, Fuchs M, Bingol N, Stone RK, Gromisch DS, Wasserman Strabismus. 1991;28:1.
E. Palpebral fissure length in black and Hispanic children: correla- 191. Tomonaga M. The quantitative visual field of children (author’s
tion with head circumference. Pediatrics. 1985;75:318–20. transl). Nippon Ganka Gakkai Zasshi. 1974;78:482–91.
179. Wang FM, Millman AL, Sidoti PA, Goldberg RB. Ocular findings 192. Lakowski R, Aspinall PA. Static perimetry in young children.
in Treacher Collins syndrome. Am J Ophthalmol. 1990;110:280–6. Vision Res. 1969;9:305–11.