Review Article
Screening, Genetics, Risk Factors, and Treatment
of Neonatal Cataracts
Jinyu Li1,2, Chun-hong Xia3, Eddie Wang3, Ke Yao1,2, and Xiaohua Gong
Neonatal cataracts remain the most common cause of visual loss in children
worldwide and have diverse, often unknown, etiologies. This review
summarizes current knowledge about the detection, treatment, genetics, risk
factors, and molecular mechanisms of congenital cataracts. We emphasize
significant progress and topics requiring further study in both clinical cataract
therapy and basic lens research. Advances in genetic screening and surgical
technologies have improved the diagnosis, management, and visual outcomes
of affected children. For example, mutations in lens crystallins and
membrane/cytoskeletal components that commonly underlie genetically
inherited cataracts are now known. However, many questions still remain
Introduction
Screening, characterization, and treatment of congenital
cataracts in children have improved in recent years due to
technological advances, including whole genome DNA
sequencing, high resolution imaging, and stem cell
research (Chan et al., 2012; Gillespie et al., 2016; Wu
et al., 2016). Visual outcomes depend on the timing of sur-
gery to remove dense cataracts (Chen et al., 2016). Despite
early surgery and aggressive optical rehabilitation, children
may still develop other ocular disorders, such as glaucoma
and nystagmus (Gasper et al., 2016).
Good vision is established postnatally and relies on the
coordinated growth and spacing of the eyeball’s optical
components, including the cornea, lens, and retina. Eye
globe length along the visual axis increases dramatically in
the first several years after birth, as does lens size. The
ocular lens is a central component of the eye’s optical sys-
tem that allows fine focusing of light onto the retina. The
growth, shape, and optical properties of the lens need to
be precisely regulated to establish good vision. However, it
remains largely unknown how lens growth in childhood is
coupled to overall eye growth to guarantee proper
1
Eye Center, Second Affiliated Hospital of Medical College, Zhejiang
University, Hangzhou, Zhejiang, China
2
Key Laboratory of Ophthalmology of Zhejiang Province, China
3
School of Optometry and Vision Science Program, University of California,
Berkeley, California, USA
Authors Li and Xia are co-first authors.
Supported by National Institutes of Health (Grant EY013849).
*Correspondence to: Xiaohua Gong, 695 Minor Hall, Berkeley, CA 94720,
USA. E-mail: xgong@berkeley.edu
Published online 0 Month 2017 in Wiley Online Library (wileyonlinelibrary.com).
Doi: 10.1002/bdr2.1050
C 2017 Wiley Periodicals, Inc.
V
*3
regarding the causes, progression, and pathology of neonatal cataracts.
Further investigations are also required to improve diagnostic criteria for
determining the timing of appropriate interventions, such as the implantation
of intraocular lenses and postoperative management strategies, to ensure
safety and predictable visual outcomes for children.
Birth Defects Research 00:000–000, 2017.
C 2017 Wiley Periodicals, Inc.
V
Key words: cataract; eye; lens; vision; development
focusing. Congenital cataracts not only impair lens trans-
parency, but can also affect lens growth and other optical
properties leading to detrimental vision loss.
Although many mutated genes and risk factors are
associated with congenital cataracts, the resulting progres-
sion of cataractogenesis and visual outcomes remains
unpredictable. The severity of congenital cataracts, associ-
ated with different or even identical mutations of the
same gene, can vary from dense opacity to clear, depend-
ing on the individual. For example, many different point
mutations of GJA8 are associated with various types of cat-
aracts (He et al., 2011); the GJA8 p.D47N mutation was
first associated with severe nuclear pulverulent cataracts
(Arora et al., 2008), but a later report showed that the
same mutation caused nuclear cataracts with incomplete
penetrance among affected individuals of the same family
(He et al., 2011). Recently, we identified an 11-year-old
child with the GJA8 p.D47N mutation displaying a very
mild, diffuse, nuclear cataract (Fig. 1). Thus, genetic var-
iance and differences in living environment seem to also
significantly affect the development of congenital cataracts.
Such uncertainties make precise diagnosis and determina-
tion of timely cataract surgery difficult.
Congenital cataracts result from disrupted lens devel-
opment or function during embryonic to postnatal stages
due to mutated genes or various other risk factors. The
lens derives from head surface ectoderm, adjacent to the
optic vesicle, which undergoes thickening to form the lens
placode that invaginates to form the lens vesicle during
the fifth week of gestation (Francis et al., 1999; McAvoy
et al., 1999; Graw, 2003; Bassnett et al., 2011; Cvekl and
Ashery-Padan, 2014). Cells in the posterior half of the lens
vesicle differentiate and elongate to form the primary lens
fibers that fill in the cavity of the lens vesicle; meanwhile,
2 NEONATAL CATARACTS

fibers overlay on older fibers from the lens surface through-

FIGURE 1. A slit lamp photo of a dilated pupil from an 11-year-old affected
child with a congenital nuclear cataract caused by the GJA8 p.D47N muta-
tion, which displays a pulverulent phenotype as previously reported (Arora
et al., 2008; He et al., 2011). The D47N mutation of connexin 50 causes
hereditary nuclear cataracts in this family with an autosomal dominant mode
of inheritance and incomplete penetrance.
cells in the anterior half of the lens vesicle remain prolifer-
ative as lens epithelial cells (LECs). Thereafter, LECs prolif-
erate especially in a region known as the germinative zone
just anterior to the lens equator (Mochizuki and Masai,
2014).
Lens growth relies on anterior LECs that are displaced
toward the posterior, eventually differentiating into second-
ary lens fibers at the lens equator. Newly formed secondary
out life as the lens grows (McAvoy et al., 1999; Cvekl and
Ashery-Padan, 2014; Mochizuki and Masai, 2014). Eventu-
ally, the tips of interior secondary fibers meet those of fibers
from an opposite hemisphere at the anterior and posterior
sutures. Fiber differentiation and elongation are accompa-
nied by the accumulation of a, b, and c-crystallins, and the
formation of membrane-cytoskeleton structures, including
surface protrusions and ball-and-sockets (McAvoy, 1978;
Willekens and Vrensen, 1982; Kuszak, 1995; Taylor et al.,
1996; Bassnett et al., 2011). Lens interior fibers transition
through several stages as they are buried progressively
deeper from the surface. Peripheral elongating fibers are
well organized and form surface ball-and-socket and protru-
sion structures, and then lose all of their organelles and
nuclei in the lens inner cortex to become mature fibers
(Bassnett, 2002).
Mature fibers further undergo tremendous surface
morphogenesis to form surface tongue-and-groove mem-
brane undulations, while becoming highly compacted
(Costello et al., 2013). A diagram of lens development is
illustrated (Fig. 2). Gene mutations and various risk factors
can disrupt certain stages of lens development or damage
lens cells of specific regions from the periphery to the lens
core, resulting in various types of human cataracts.
The human lens grows exponentially before birth and
in infancy (Gordon and Donzis, 1985; Bours and F€ odisch,
1986; Augusteyn, 2007; Augusteyn et al., 2012). However,
lens thickness seems relatively unchanged early in life
(Pennie et al., 2001; Mutti et al., 2005; Trivedi and Wilson,
2007). Both axial length and lens thickness have been

FIGURE 2. Lens and fiber cell development. (A) The lens vesicle is a hollow cell-lined structure that forms in the fifth week of gestation. Cells at the posterior half
of the vesicle differentiate and elongate toward the anterior. (B) The elongated primary fiber cells fill the vesicle cavity while the cells at the anterior become lens
epithelial cells (LECs). (C) The lens grows by proliferation of LECs, especially in the germinative zone (GZ). LECs near the equator differentiate into new fiber cells,
elongate, and surround older fibers (blue cortical fibers). Eventually the fibers lose their nuclei and undergo compaction (yellow mature fibers). The original fibers
from the embryonic lens remain in the core of the lens.
BIRTH DEFECTS RESEARCH 00:00–00 (2017)
found to be shorter in cases of congenital cataract (Kugel-
berg et al., 1996; Trivedi and Wilson, 2007). Lens and eye
biometry has been performed in utero using ultrasound
and MRI (Sukonpan and Phupong, 2009; Velasco-Annis
et al., 2015). Pediatric eye biometry is performed with
contact or noncontact ultrasonography or partial coher-
ence interferometry (Al Shamrani and Al Turkmani, 2012).
Of interest, the rate of axial length growth seems unal-
tered by intraocular lens (IOL) implantation (Sminia et al.,
2010). However, molecular and cellular mechanisms
describing how lens growth and shape are regulated to
couple with postnatal visual experience remain elusive.
Prevalence and Epidemiological Characteristics
of Congenital Cataract
Congenital cataract refers to a lens opacity present at birth
or detected within the first year of life. Studies on the preva-
lence of congenital cataracts have been conducted in differ-
ent regions and populations with various epidemiological
characteristics; the numbers are quite variable from study
to study, due to regional and socioeconomic factors. For
examples, one study estimated that approximately 200,000
children are blind due to congenital cataracts globally (Fos-
ter et al., 1997); another reported a prevalence of 1 to 15
per 10,000 children worldwide, and from 1 to 3 per 10,000
births in developing countries (Lin et al., 2014); while a
third study found the prevalence of childhood cataract to be
0.42 to 2.05 per 10,000 kids in developing countries, com-
pared with 0.63 to 13.6 per 10,000 children in developed
countries (Sheeladevi et al., 2016).
A recent systematic review and meta-analysis calculated
a pooled estimate of congenital cataract prevalence, based
on 17 population studies of 8,302,708 children, from
regions including Asia, Europe, Australia, Africa, and the
United States, spanning from 1959 to 2010 (Wu et al.,
2016). The pooled value was 4.24 cases per 10,000 children
and considered the effects of diagnosis age, sample size,
research period, and included study quality (Wu et al.,
2016). Delayed diagnosis of affected children in developing
countries makes more accurate estimates difficult. Regard-
less, the prevalence and life-long effects of childhood blind-
ness have made it a priority of the global vision 2020
initiative (World Health Organization Global Initiative for
the Elimination of Avoidable Blindness, 1997 WHO, Geneva,
publication no. PBL/97.61).
Congenital cataracts have diverse etiologies with many
unknown causes (Chan et al., 2012). The pooled estimates
indicate that the majority of congenital cataracts are idio-
pathic (62.2%), while hereditary and nonhereditary causes
accounted for 22.3% and 11.5% of cases, respectively (Wu
et al., 2016). Genetic abnormalities, such as chromosomal
trisomies (trisomy 13; trisomy 18, Edwards syndrome;
trisomy 21, Down’s syndrome), are also causes for congen-
ital cataracts (Pe’er and Braun, 1986; Catalano, 1990;
3
Lueder, 2006). With advances in genetic mapping and DNA
sequencing technologies, a large number of human here-
ditary cataracts has been linked to mutations in genes
encoding lens crystallins, connexins, aquaporin, cytos-
keletal structural proteins, and other key regulators of
lens development.
Many childhood cataracts are isolated, while some are
accompanied by ocular and systemic disorders. For ocular
disorders, congenital aniridia (Zhang et al., 2017), microcor-
nea (congenital microcornea-cataract syndrome) (Leng
et al., 2016), microphthalmia (Kondo et al., 2013), persistent
hyperplastic primary vitreous (Prasov et al., 2012), Marfan
syndrome (Khosravi et al., 2014), and Marchesani syndrome
(Steinkellner et al., 2015) are most common. Systemic disor-
ders most commonly associated with congenital cataracts
are congenital heart disease and nervous system disease.
Other congenital cataract associated syndromes, such as
Hallermann-Streiff-Francois syndrome (Pasyanthi et al.,
2016), Wolfram syndrome (Morikawa et al., 2017), congeni-
tal cataract facial dysmorphism neuropathy syndrome (Mas-
ters et al., 2017), Nance-Horan syndrome (NHS) (Tian et al.,
2017), and Lowe syndrome (Gao et al., 2016) have also
been reported. Ocular manifestations can result from inher-
ited metabolic disorders (Rajappa et al., 2010), including
galactosemia (Lee et al., 1995), Wilson disease, hypocalce-
mia, hypo/hyperglycemia, and Lowe syndrome. Thus,
genetic counseling and molecular testing could be very help-
ful in such cases (Santana and Waiswo, 2011).
Trauma and various diseases often cause nonhereditary
congenital cataracts. Some congenital cataracts can be caused
by intrauterine infections, such as rubella virus, herpes sim-
plex virus, toxoplasma gondii, cytomegalovirus, syphilis, and
varicella zoster virus (Dewan and Gupta, 2012; Jyoti et al.,
2015; Singh et al., 2016), and, therefore, it is necessary to carry
out conventional TORCH tests (toxoplasma, rubella virus, cyto-
megalovirus, HSV, and others) in pregnant women (Mc Loone
et al., 2016). In addition, malnutrition during pregnancy
(Kumar et al., 2013), radiographic exposure (Shore et al.,
2010), medicines such as linezolid (Ilarslan et al., 2014), and
intrauterine hypoxia can cause childhood cataracts.
Postnatal cataracts can be unilateral and bilateral, based
on several systematic studies (Rahi and Dezateux, 2000;
Wirth et al., 2002; Wu et al., 2016). The cataracts can be
morphologically classified as total, nuclear, posterior sub-
capsular, anterior polar, posterior polar, zonular, nuclear,
lamellar, pulverulent, sutural, cerulean, corraliform, or poly-
morphic (Hejtmancik, 2008). Morphology subtype analysis
indicated that total and nuclear cataracts were the most
common congenital cataracts (Perucho-Martinez et al.,
2007). A better understanding of the prevalence, epidemio-
logical characteristics, and underlying mechanisms of child-
hood cataracts may lead to the identification of prevention
factors or strategies for improving visual function after cata-
ract surgery.
4 NEONATAL CATARACTS
Screening Techniques and the Future
of Prenatal Diagnosis
Early diagnosis is essential for effectively managing con-
genital cataracts; left untreated, visual deprivation can
damage the developing visual system of a child. Red reflex
examination at birth is an easy method to screen for con-
genital cataracts; it is recommended to perform direct
ophthalmoscopy to check for light reflex and red reflex in
newborn babies after birth (Mansoor et al., 2016; Rajavi
and Sabbaghi, 2016). Early detection is important for facil-
itating genetic counseling and timely treatment. Moreover,
both genetic and mechanistic studies of congenital cata-
racts will allow clinicians to better understand cataract
development and to determine surgery timelines that will
reduce or prevent postsurgical vision complications.
Great progress has been made in screening for congen-
ital cataracts using techniques, such as candidate gene
approach, linkage analysis, DNA probe microarrays, and
gene sequencing. Next-generation sequencing approaches,
including genome sequencing, whole exome sequencing,
and select target enrichment (Gillespie et al., 2016), have
been used in the diagnosis of pediatric cataracts (Musleh
et al., 2016; Liu et al., 2017).
Prenatal genetic diagnosis can be provided for a fetus
at early gestational stages through chorionic villus or
amniotic fluid sampling by invasive operations. However,
traditional invasive methods pose a risk to the mother and
unborn fetus. Genetic screening of fetal cells from the cer-
vix or fetal cells from peripheral blood by noninvasive
operations may be more safe and effective. Noninvasive
prenatal testing (NIPT) is a new method that determines
the genomic status of a fetus in utero by analyzing circu-
lating fetal DNA in maternal plasma or serum. Current
advances in diagnostic NIPT will have significant impacts
on all prenatal testing (Liu et al., 2016).
Genetics of Congenital Cataracts and Childhood
Risk Factors
Congenital cataracts display huge variation clinically and
genetically, and can be associated with mutations, genetic
variance, and other risk factors. As previously mentioned,
the prevalence and incidence of congenital cataracts varies
widely among different regions or countries (Francois,
1982; Meinel, 1991; Haargaard et al., 2005). The majority
of inherited congenital cataracts displays autosomal
dominant inheritance, but some cataracts are inherited
according to an autosomal recessive, X-linked, or even
mitochondrial DNA mode of inheritance. Affected patients
often show bilateral symmetrical cataracts with variable
severity.
Advances in genetic linkage analysis, exome sequenc-
ing, and new high-throughput DNA sequencing technolo-
gies have greatly expanded our knowledge of cataracts
causing gene mutations. Growing knowledge about the
gene regulatory networks for lens cell proliferation, differ-
entiation, elongation, and maturation during development,
as well as about metabolites required for lens homeosta-
sis, provides molecular and cellular insights into the basis
of many cataracts (Mathias et al., 2010; Bassnett et al.,
2011). Congenital cataracts result from mutations of genes
encoding proteins needed for normal lens structure, func-
tion, and homeostasis. The mutations generate missense,
nonsense, or deletion variants, and can also alter splicing
sites and introns. Mutations of genes functioning in
embryonic or early lens development usually lead to
nuclear cataracts: opacities in the lens core. Other gene
mutations, systemic diseases, and trauma can cause corti-
cal cataracts: opacities appearing in lens peripheral fibers.
In recent years, the number of genes and mutations
that are associated with congenital cataracts has greatly
expanded and is nicely summarized in this Web site: Cat-
Map, http://cat-map.wustl.edu/ (Shiels et al., 2010). To
date, congenital cataracts have been associated with muta-
tions of genes encoding crystallins (almost half of muta-
tions), lens membrane proteins such as connexins or
aquaporin 0 (MIP26 or MP26), various growth or tran-
scription factors, cytoskeletal components such as interme-
diate filament proteins, other membrane proteins, or
proteins in degradation pathways. Less than 10% of the
mutations occur in other proteins, including those of lipid
metabolism (Shiels et al., 2010).
CRYSTALLIN GENE MUTATIONS
It is not surprising that crystallin gene mutations account
for almost 50% of all autosomal dominant cataracts. Crys-
tallins are the major structural proteins in the lens, mak-
ing up 90% of lens soluble proteins. Lens crystallin
proteins consist of a-, b-, and c- isoforms, encoded by dif-
ferent genes. Mutations have been identified in the follow-
ing crystallin genes: CRYAA, CRYAB, CRYBB1, CRYBB2,
CRYBB3, CRYBA1, CRYGC, CRYGD, and CRYGS (Cat-Map,
http://cat-map.wustl.edu/) (Shiels and Hejtmancik, 2015).
At least 17 different mutations of CRYAA, and 10 different
mutations of CRYAB have been identified to cause congeni-
tal cataracts. CRYAA and CRYAB encode aA- and aB-
crystallins, respectively, members of the small heat-shock
protein (sHSP) family with chaperone-like activities (Hor-
witz, 1992; Clark et al., 2012). CRYAA mutations mostly
cause nuclear cataracts. CRYAB mutations are associated
with cataracts but are also linked to cardiac myopathies
due to high expression in cardiomyocytes. Among all genes
encoding b-crystallins and c-crystallins, CRYBB2 and
CRYGD genes include the majority of identified mutations.
LENS MEMBRANE PROTEIN GENE MUTATIONS
Mutations of connexins, components of intercellular gap
junction channels, are the second most abundant gene
mutations causing congenital cataracts (Cat-Map, http://
cat-map.wustl.edu/). The avascular lens depends on gap
BIRTH DEFECTS RESEARCH 00:00–00 (2017)
junction channels to transport small molecules, such as
ions, nutrients, and metabolites, between adjacent cells to
maintain metabolic homeostasis and transparency
(Mathias et al., 2010). Gap junction channels in lens fiber
cells are mainly formed by gap junction proteins connexin-
46 and connexin-50, encoded by GJA3 and GJA8, respectively
(Gong et al., 2007). Many missense and frameshift muta-
tions of GJA3 and GJA8 have been identified in members of
families with inherited cataracts, typically autosomal-
dominant nuclear and zonular pulverulent cataracts
(Mackay et al., 1999; Rees et al., 2000; Yao et al., 2011; Zhu
et al., 2014; Yu et al., 2016). Functional studies of some
mutant connexin proteins have revealed that mutations
cause altered gap junction properties and altered cell sur-
face expression, thus compromising intercellular communi-
cation and resulting in lens opacities (Gao et al., 2004; Beyer
et al., 2013; Yu et al., 2016).
Lens major intrinsic protein (MIP), also named as
aquaporin 0 or MP26, is an integral membrane protein
that functions as a channel for water transport and plays
an important cell to cell adhesion role. Identified MIP
mutations cause mostly autosomal dominant cataracts.
Abnormal retention of mutant MIP within the endoplasmic
reticulum was previously reported (Shiels, 2012; Lo et al.,
2014). Lens intrinsic membrane protein 2 (LIM2 or MP20)
is a transmembrane protein, and has a role in cell adhe-
sion, junction formation, and the formation of the lens
core syncytium. Several LIM2 mutations were identified
and associated with autosomal recessive cataracts (Shi
et al., 2009; Maher et al., 2012).
Mutations of SLC16A12, a transmembrane transporter
active in monocarboxylic acid transport, can cause domi-
nant cataracts (Cat-Map, http://cat-map.wustl.edu/).
Cataract caused by EPHA2 gene mutations are also
abundant; more than 20 mutations of EPHA2 have been
found in both dominant and recessive inherited cataracts
(Cat-Map, http://cat-map.wustl.edu/). EPHA2 encodes a
member of the ephrin receptor subfamily of protein-
tyrosine kinases, which plays a role in lens cell migration
through interaction with src kinase. Mutations might
destabilize the receptor (Park et al., 2012; Shi et al., 2012;
Cheng et al., 2013).
LENS CYTOSKELETON GENE MUTATIONS
A network of various lens cytoskeletal proteins maintains
cell shape and size. Lens cells contain three filaments:
microfilaments, microtubules, and intermediate filaments.
Intermediate filaments of lens cells are important not only
for supporting fiber cell structures and organization, but
also for maintaining lens integrity and stability during lens
accommodation.
Beaded filament structural proteins (BFSPs) form the
unique lens-specific intermediate filaments. Two core com-
ponents are encoded by BFSP1 (filensin) and BFSP2
(CP49), these two BFSPs combine with a-crystallin to form
5
beaded-filament structures only found in lens fiber cells
(Song et al., 2009). Mutations in BFSP1 and BFSP2 have
been identified in both autosomal dominant and recessive
cataracts; nuclear or lamellar cataracts usually appeared in
the dominant cases while cortical cataracts tended to form
in the recessive cases. Vimentin is another intermediate fil-
ament protein highly expressed in lens peripheral fiber
cells; a few vimentin gene mutations have been identified
to be associated with inherited cataracts (Muller et al.,
2009; Ma et al., 2016). A recent study revealed a mutation
of the PRX gene, encoding a cytoskeletal scaffold protein,
periaxin, to be associated with congenital cataract (Yuan
et al., 2016).
FYCO1 encodes a scaffolding protein active in microtu-
bule based transport of autophagic vesicles. Multiple
FYCO1 mutations have been identified and associated with
autosomal recessive cataracts (Cat-Map, http://cat-map.
wustl.edu/) (Chen et al., 2011). Many NHS mutations have
been linked to congenital cataracts (Cat-Map); NHS enco-
des a regulator of actin remodeling and cell shape, and
mutations cause X-linked cataract in males and mild
sutural opacities in females (Coccia et al., 2009; Brooks
et al., 2010). Thus, dynamic regulation of cytoskeletal fila-
ments and their associated scaffold proteins are critical for
lens development and transparency.
OTHER LENS GENE MUTATIONS
The PAX6 gene encodes a transcription factor with a highly
conserved homeodomain that is important for eye develop-
ment. Its mutations result in autosomal-dominant aniridia, a
syndrome including cataracts (Zhang et al., 2011).
Close to 20 mutations of HSF4 are associated with both
autosomal-dominant and recessive cataracts (Cat-Map,
http://cat-map.wustl.edu/). HSF4 regulates transcription of
heat-shock proteins, including CRYAB (Somasundaram and
Bhat, 2004). Some cataracts can be caused by gene muta-
tions in other transcription factors, including PITX3, FOXE3,
and MAF (Cat-Map, http://cat-map.wustl.edu/). In addition,
large numbers of mutations of the ferritin light chain gene,
FTL, are associated with hyperferritinemia-cataract syn-
drome (Cat-Map, http://cat-map.wustl.edu/), and the cata-
racts are associated with hyperferritinemia without iron
overload (Girelli et al., 1995).
Cataract Surgery and Concerns
Early diagnosis for neonatal cataracts is important for
achieving good visual function, which largely depends on
the timing of surgery to remove dense cataracts (Chan
et al., 2012). With the development of surgical techniques,
microincision cataract extraction combined with primary
IOL implantation has been accepted as the primary
method for the management of childhood cataract (Wang
and Xiao, 2015). Surgical intervention is also crucial to
prevent irreversible amblyopia caused by congenital cata-
ract (Chen et al., 2016).
6 NEONATAL CATARACTS
Because of children’s special anatomical features and
severe inflammatory response, pediatric cataract surgery
remains complex and challenging. The timing of surgery
needs to balance the effect on visual development and the
surgical risks. Neonatal cataract removal should be per-
formed early enough to prevent the onset of deprivation
amblyopia, particularly in the unilateral cases. Infants
younger than 6 months ought to accept cataract extraction,
combined with primary posterior continuous curvilinear
capsulorrhexis and anterior vitrectomy (Nagamoto et al.,
2015). There is increasing evidence of safety for IOL implan-
tation in those younger than two years of age; however, it
remains controversial what the best age is for IOL implanta-
tion (Chen et al., 2016). Primary IOL implantation is a stand-
ard procedure for patients older than two years of age. In
terms of unilateral cataracts, primary IOL implantation is
suggested to be carried out in patients over 1 year old
(Tadros et al., 2016). IOL implantation in children less than
6 months old, particularly in bilateral cataracts, is still con-
sidered high risk due to severe postoperative inflammation,
posterior capsule opacification (PCO), and other complica-
tions (Vasavada and Vasavada, 2017).
The selection of IOLs is the most contentious and key
issue, which depends on the optical factors of the operated
eye; various measurements such as accurate estimation of
axial length, corneal curvature and refraction, and compre-
hensive evaluation of IOL and power selection (Al Shamrani
and Al Turkmani, 2012). Foldable hydrophobic acrylic IOL
material is widely used, as it maintains centration and causes
less severe PCO and inflammation (Wilson et al., 2007). Axial
length can be measured using contact or immersion ultraso-
nography or optical biometry. Measurement error by these
methods may play a role in clinically residual refractive error
(Wilson and Trivedi, 2012). Among all the IOL calculation for-
mulas, the Hoffer Q formulas were reported to be more accu-
rate than others for children, especially in eyes shorter than
22 mm (Kane et al., 2016).
Clinical ophthalmologists aim to choose the appropriate
IOL to gain the targeted postoperative refraction state, while
taking the myopic shift into account. Younger children at
time of implantation show greater myopic shift. To reduce
the necessity of IOL exchange, patients should be undercor-
rected by 10 to 20%, with the residual refractive error cor-
rected by spectacles that are continually adjusted
throughout life, according to refractive development (Dahan
and Drusedau, 1997). In terms of the type of IOLs, the poste-
rior chamber IOLs in-the-bag implantation is most recom-
mended in pediatric aphakic eyes (Luo et al., 2013), anterior
chamber IOLs and iris-fixated IOLs may be used in some
children who have inadequate capsular support, but are
unlikely to be widely adopted (Barbara et al., 2016).
Common complications of childhood cataract surgery
include PCO, secondary glaucoma, uveitis, pupil displace-
ment, IOL pupillary capture, and decentration (Gasper
et al., 2016); they are often related to aggressive
inflammatory reaction, etiology of the cataract, and the
age of the patient (Whitman and Vanderveen, 2014). PCO
is the most common complication of cataract surgery with
a risk of nearly 95%, and is associated with abnormal pro-
duction of inflammatory factors (Fan et al., 2006). Preven-
tion of PCO is a major task faced by the entire pediatric
ophthalmology community. Both the in-the-bag IOL fixa-
tion and surgical technique influence the prevalence of
PCO. Primary posterior capsulotomy and anterior vitrec-
tomy are considered routine surgical steps, especially in
children younger than two years old (Vasavada et al.,
2011).
Treatment with dexamethasone or cytoskeletal drugs
was reported to inhibit PCO formation in human lens cap-
sules in vitro (Sureshkumar et al., 2012). Newly designed
IOLs embedded with slow-release molecules may reduce
inflammation and the need for topical anti-inflammatory
treatment (Kugelberg et al., 2010). Posterior capsulotomy
with Nd:YAG laser treatment is an effective way to elimi-
nate PCO (Chen and Fredrick, 2010). Secondary glaucoma
is another common complication after lensectomy (Baden
et al., 2013). Diagnosis of glaucoma following congenital
cataract surgery requires lifelong surveillance (Ma et al.,
2012). Moreover, a standardized amblyopia training pro-
gram with long-term follow-up is essential for visual reha-
bilitation after congenital cataract surgery (Repka, 2016).
Due to postsurgical complications, congenital cataracts
remain the leading cause for childhood blindness, thus
new therapeutic strategies need to be explored. A recent
study reported a novel strategy to restore lens transpar-
ency and visual function by using regeneration of endoge-
nous lens stem cells (Lin et al., 2016). It is too early to
judge whether endogenous stem cells from a cataractous
lens would eventually generate a clear lens that could
properly focus images onto the retina.
In summary, significant advances in DNA sequencing
technologies, personalized diagnosis, and genetic counsel-
ing have continually reduced childhood blindness due to
congenital cataracts. However, noninvasive prenatal diag-
nosis, and new surgical procedures in conjunction with
lens regeneration techniques will be important for treating
or preventing congenital cataracts in affected younger chil-
dren. Perhaps, future studies in both lens regeneration
and inhibition of neonatal cataracts would lead to effective
strategies for not only treating congenital cataracts, but
also restoring visual function.
Acknowledgments
X.G. was supported by the National Institutes of Health. The
authors declare no conflict of interest.
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