Skip to main content
NCBI home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2022 Jun 21.
Published in final edited form as: Birth Defects Res. 2017 May 22;109(10):734–743. doi: 10.1002/bdr2.1050

Screening, Genetics, Risk Factors, and Treatment of Neonatal Cataracts

Jinyu Li 1,2, Chun-hong Xia 3, Eddie Wang 3, Ke Yao 1,2, Xiaohua Gong 3,*
PMCID: PMC9211061  NIHMSID: NIHMS1817227  PMID: 28544770

Abstract

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 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.

Keywords: cataract, eye, lens, vision, development

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 surgery 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 system 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 focusing. Congenital cataracts not only impair lens transparency, 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 progression of cataractogenesis and visual outcomes remains unpredictable. The severity of congenital cataracts, associated with different or even identical mutations of the same gene, can vary from dense opacity to clear, depending on the individual. For example, many different point mutations of GJA8 are associated with various types of cataracts (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 variance and differences in living environment seem to also significantly affect the development of congenital cataracts. Such uncertainties make precise diagnosis and determination of timely cataract surgery difficult.

FIGURE 1.

FIGURE 1.

Open in a new tab

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 mutation, 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.

Congenital cataracts result from disrupted lens development 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, cells in the anterior half of the lens vesicle remain proliferative as lens epithelial cells (LECs). Thereafter, LECs proliferate 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 secondary lens fibers at the lens equator. Newly formed secondary fibers overlay on older fibers from the lens surface throughout life as the lens grows (McAvoy et al., 1999; Cvekl and Ashery-Padan, 2014; Mochizuki and Masai, 2014). Eventually, 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 accompanied by the accumulation of α, β, and γ-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 protrusion 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 membrane 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.

FIGURE 2.

FIGURE 2.

Open in a new tab

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.

The human lens grows exponentially before birth and in infancy (Gordon and Donzis, 1985; Bours and Födisch, 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 found to be shorter in cases of congenital cataract (Kugelberg 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 coherence interferometry (Al Shamrani and Al Turkmani, 2012). Of interest, the rate of axial length growth seems unaltered 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 prevalence of congenital cataracts have been conducted in different 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 (Foster 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, compared 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. Regardless, the prevalence and life-long effects of childhood blindness 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 idiopathic (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 congenital cataracts (Pe’er and Braun, 1986; Catalano, 1990; Lueder, 2006). With advances in genetic mapping and DNA sequencing technologies, a large number of human hereditary cataracts has been linked to mutations in genes encoding lens crystallins, connexins, aquaporin, cytoskeletal 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), microcornea (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 disorders 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), congenital cataract facial dysmorphism neuropathy syndrome (Masters 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 inherited metabolic disorders (Rajappa et al., 2010), including galactosemia (Lee et al., 1995), Wilson disease, hypocalcemia, hypo/hyperglycemia, and Lowe syndrome. Thus, genetic counseling and molecular testing could be very helpful 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 simplex 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, cytomegalovirus, 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 subcapsular, anterior polar, posterior polar, zonular, nuclear, lamellar, pulverulent, sutural, cerulean, corraliform, or polymorphic (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, epidemiological characteristics, and underlying mechanisms of childhood cataracts may lead to the identification of prevention factors or strategies for improving visual function after cataract surgery.

Screening Techniques and the Future of Prenatal Diagnosis

Early diagnosis is essential for effectively managing congenital 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 congenital 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 facilitating genetic counseling and timely treatment. Moreover, both genetic and mechanistic studies of congenital cataracts 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 congenital 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 cervix 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 circulating 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 sequencing, and new high-throughput DNA sequencing technologies have greatly expanded our knowledge of cataracts causing gene mutations. Growing knowledge about the gene regulatory networks for lens cell proliferation, differentiation, elongation, and maturation during development, as well as about metabolites required for lens homeostasis, 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, function, 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 cortical 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 mutations of genes encoding crystallins (almost half of mutations), lens membrane proteins such as connexins or aquaporin 0 (MIP26 or MP26), various growth or transcription factors, cytoskeletal components such as intermediate 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. Crystallins are the major structural proteins in the lens, making up ~90% of lens soluble proteins. Lens crystallin proteins consist of α-, β-, and γ- isoforms, encoded by different genes. Mutations have been identified in the following 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 congenital cataracts. CRYAA and CRYAB encode αA- and αB-crystallins, respectively, members of the small heat-shock protein (sHSP) family with chaperone-like activities (Horwitz, 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 β-crystallins and γ-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 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 mutations 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 surface expression, thus compromising intercellular communication 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 adhesion, 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 dominant 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 components are encoded by BFSP1 (filensin) and BFSP2 (CP49), these two BFSPs combine with α-crystallin to form 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 filament 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 microtubule 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 encodes 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 filaments 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 development. 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 mutations 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 syndrome (Cat-Map, http://cat-map.wustl.edu/), and the cataracts 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 cataract (Chen et al., 2016).

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 performed 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 implantation in those younger than two years of age; however, it remains controversial what the best age is for IOL implantation (Chen et al., 2016). Primary IOL implantation is a standard 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 considered high risk due to severe postoperative inflammation, posterior capsule opacification (PCO), and other complications (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 comprehensive 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 ultrasonography 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 formulas, the Hoffer Q formulas were reported to be more accurate 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 undercorrected by 10 to 20%, with the residual refractive error corrected by spectacles that are continually adjusted throughout life, according to refractive development (Dahan and Drusedau, 1997). In terms of the type of IOLs, the posterior chamber IOLs in-the-bag implantation is most recommended 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 displacement, 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 production of inflammatory factors (Fan et al., 2006). Prevention of PCO is a major task faced by the entire pediatric ophthalmology community. Both the in-the-bag IOL fixation and surgical technique influence the prevalence of PCO. Primary posterior capsulotomy and anterior vitrectomy 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 capsules 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 eliminate 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 program with long-term follow-up is essential for visual rehabilitation 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 transparency and visual function by using regeneration of endogenous 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 counseling have continually reduced childhood blindness due to congenital cataracts. However, noninvasive prenatal diagnosis, and new surgical procedures in conjunction with lens regeneration techniques will be important for treating or preventing congenital cataracts in affected younger children. 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.

Supported by National Institutes of Health (Grant EY013849).

References

  1. Al Shamrani M, Al Turkmani S. 2012. Update of intraocular lens implantation in children. Saudi J Ophthalmol 26:271–275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arora A, Minogue PJ, Liu X, et al. 2008. A novel connexin50 mutation associated with congenital nuclear pulverulent cataracts. J Med Genet 45:155–160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Augusteyn RC. 2007. Growth of the human eye lens. Mol Vis 13:252–257. [PMC free article] [PubMed] [Google Scholar]
  4. Augusteyn RC, Nankivil D, Mohamed A, et al. 2012. Human ocular biometry. Exp Eye Res 102C:70–75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Baden C, Shija F, Lewallen S, et al. 2013. Glaucoma after pediatric cataract surgery in a population with limited access to care. J AAPOS 17:158–162. [DOI] [PubMed] [Google Scholar]
  6. Barbara R, Rufai SR, Tan N, Self JE. 2016. Is an iris claw IOL a good option for correcting surgically induced aphakia in children? A review of the literature and illustrative case study. Eye 30:1155–1159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bassnett S 2002. Lens organelle degradation. Exp Eye Res 74:1–6. [DOI] [PubMed] [Google Scholar]
  8. Bassnett S, Shi Y, Vrensen GF. 2011. Biological glass: structural determinants of eye lens transparency. Philos Trans R Soc Lond B Biol Sci 366:1250–1264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Beyer EC, Ebihara L, Berthoud VM. 2013. Connexin mutants and cataracts. Front Pharmacol 4:43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Bours J, Födisch HJ. 1986. Human fetal lens: wet and dry weight with increasing gestational age. Ophthalmic Res 18:363–368. [DOI] [PubMed] [Google Scholar]
  11. Brooks SP, Coccia M, Tang HR, et al. 2010. The Nance-Horan syndrome protein encodes a functional WAVE homology domain (WHD) and is important for co-ordinating actin remodelling and maintaining cell morphology. Hum Mol Genet 19:2421–2432. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Catalano RA. 1990. Down syndrome. Surv Ophthalmol 34:385–398. [DOI] [PubMed] [Google Scholar]
  13. Chan WH, Biswas S, Ashworth JL, Lloyd IC. 2012. Congenital and infantile cataract: aetiology and management. Eur J Pediatr 171:625–630. [DOI] [PubMed] [Google Scholar]
  14. Chen J, Ma Z, Jiao X, et al. 2011. Mutations in FYCO1 cause autosomal-recessive congenital cataracts. Am J Hum Genet 88:827–838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Chen JA, Fredrick DR. 2010. Novel technique for Nd:YAG posterior capsulotomy in pediatric patients. J Pediatr Ophthalmol Strabismus 47:41–42. [DOI] [PubMed] [Google Scholar]
  16. Chen W, Long E, Chen J, et al. 2016. Timing and approaches in congenital cataract surgery: a randomised controlled trial. Lancet 388(Suppl 1):S52. [Google Scholar]
  17. Cheng C, Ansari MM, Cooper JA, Gong X. 2013. EphA2 and Src regulate equatorial cell morphogenesis during lens development. Development 140:4237–4245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Clark AR, Lubsen NH, Slingsby C. 2012. sHSP in the eye lens: crystallin mutations, cataract and proteostasis. Int J Biochem Cell Biol 44:1687–1697. [DOI] [PubMed] [Google Scholar]
  19. Coccia M, Brooks SP, Webb TR, et al. 2009. X-linked cataract and Nance-Horan syndrome are allelic disorders. Hum Mol Genet 18:2643–2655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Costello MJ, Mohamed A, Gilliland KO, et al. 2013. Ultrastructural analysis of the human lens fiber cell remodeling zone and the initiation of cellular compaction. Exp Eye Re 116:411–418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Cvekl A, Ashery-Padan R. 2014. The cellular and molecular mechanisms of vertebrate lens development. Development 141:4432–4447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Dahan E, Drusedau MU. 1997. Choice of lens and dioptric power in pediatric pseudophakia. J Cataract Refract Surg 23(Suppl 1): 618–623. [DOI] [PubMed] [Google Scholar]
  23. Dewan P, Gupta P. 2012. Burden of Congenital Rubella Syndrome (CRS) in India: a systematic review. Indian Pediatr 49:377–399. [DOI] [PubMed] [Google Scholar]
  24. Fan DS, Yip WW, Yu CB, et al. 2006. Updates on the surgical management of paediatric cataract with primary intraocular lens implantation. Ann Acad Med Singapore 35:564–570. [PubMed] [Google Scholar]
  25. Foster A, Gilbert C, Rahi J. 1997. Epidemiology of cataract in childhood: a global perspective. J Cataract Refract Surg 23(Suppl 1):601–604. [DOI] [PubMed] [Google Scholar]
  26. Francis PJ, Berry V, Moore AT, Bhattacharya S. 1999. Lens biology: development and human cataractogenesis. Trends Genet 15:191–196. [DOI] [PubMed] [Google Scholar]
  27. Francois J 1982. Genetics of cataract. Ophthalmologica 184:61–71. [DOI] [PubMed] [Google Scholar]
  28. Gao J, Sun X, Martinez-Wittinghan FJ, et al. 2004. Connections between connexins, calcium, and cataracts in the lens. J Gen Physiol 124:289–300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Gao Y, Jiang F, Ou ZY. 2016. Novel OCRL1 gene mutations in six Chinese families with Lowe syndrome. World J Pediatr 12:484–488. [DOI] [PubMed] [Google Scholar]
  30. Gasper C, Trivedi RH, Wilson ME. 2016. Complications of pediatric cataract surgery. Dev Ophthalmol 57:69–84. [DOI] [PubMed] [Google Scholar]
  31. Gillespie RL, Urquhart J, Anderson B, et al. 2016. Next-generation sequencing in the diagnosis of metabolic disease marked by pediatric cataract. Ophthalmology 123:217–220. [DOI] [PubMed] [Google Scholar]
  32. Girelli D, Olivieri O, De Franceschi L, et al. 1995. A linkage between hereditary hyperferritinaemia not related to iron overload and autosomal dominant congenital cataract. Br J Haematol 90:931–934. [DOI] [PubMed] [Google Scholar]
  33. Gong X, Cheng C, Xia H. 2007. Connexins in lens development and cataractogenesis. J Membr Biol 218:9–12. [DOI] [PubMed] [Google Scholar]
  34. Gordon RA, Donzis PB. 1985. Refractive development of the human eye. Arch Ophthalmol 103:785–789. [DOI] [PubMed] [Google Scholar]
  35. Graw J 2003. The genetic and molecular basis of congenital eye defects. Nat Rev Genet 4:876–888. [DOI] [PubMed] [Google Scholar]
  36. Haargaard B, Wohlfahrt J, Rosenberg T, et al. 2005. Risk factors for idiopathic congenital/infantile cataract. Invest Ophthalmol Vis Sci 46:3067–3073. [DOI] [PubMed] [Google Scholar]
  37. He W, Li X, Chen J, et al. 2011. Genetic linkage analyses and Cx50 mutation detection in a large multiplex Chinese family with hereditary nuclear cataract. Ophthalmic Genet 32:48–53. [DOI] [PubMed] [Google Scholar]
  38. Hejtmancik JF. 2008. Congenital cataracts and their molecular genetics. Semin Cell Dev Biol 19:134–149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Horwitz J 1992. Alpha-crystallin can function as a molecular chaperone. Proc Natl Acad Sci USA 89:10449–10453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Ilarslan E, AydEn B, Kabatas EU, et al. 2014. Cataract in a preterm newborn: a possible side effect of linezolid therapy. J Coll Physicians Surg Pak 24(Suppl 3):S281–S283. [PubMed] [Google Scholar]
  41. Jyoti M, Shirke S, Matalia H. 2015. Congenital rubella syndrome: Global issue. J Cataract Refract Surg 41:1127. [DOI] [PubMed] [Google Scholar]
  42. Kane JX, Van Heerden A, Atik A, Petsoglou C. 2016. Intraocular lens power formula accuracy: Comparison of 7 formulas. J Cataract Refract Surg 42:1490–1500. [DOI] [PubMed] [Google Scholar]
  43. Khosravi A, Behjati M, Nilforoush P, et al. 2014. A case of Marfan’s syndrome with multi-level aortic dissections. ARYA Atheroscler 10:334–338. [PMC free article] [PubMed] [Google Scholar]
  44. Kondo H, Tahira T, Yamamoto K, Tawara A 2013. Familial acorea, microphthalmia and cataract syndrome. Br J Ophthalmol 97:1155–1160. [DOI] [PubMed] [Google Scholar]
  45. Kugelberg M, Shafiei K, van der Ploeg I, Zetterstrom C 2010. Intraocular lens as a drug delivery system for dexamethasone. Acta Ophthalmol 88:241–244. [DOI] [PubMed] [Google Scholar]
  46. Kugelberg U, Zetterström C, Syrén-Nordqvist S 1996. Ocular axial length in children with unilateral congenital cataract. Acta Ophthalmol Scand 74:220–223. [DOI] [PubMed] [Google Scholar]
  47. Kumar D, Lim JC, Donaldson PJ. 2013. A link between maternal malnutrition and depletion of glutathione in the developing lens: a possible explanation for idiopathic childhood cataract? Clin Exp Optom 96:523–528. [DOI] [PubMed] [Google Scholar]
  48. Kuszak JR. 1995. The ultrastructure of epithelial and fiber cells in the crystalline lens. Int Rev Cytol 163:305–350. [DOI] [PubMed] [Google Scholar]
  49. Lee AY, Chung SK, Chung SS. 1995. Demonstration that polyol accumulation is responsible for diabetic cataract by the use of transgenic mice expressing the aldose reductase gene in the lens. Proc Natl Acad Sc U S A 92:2780–2784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Leng XY, Li HY, Wang J, et al. 2016. Congenital microcornea-cataract syndrome-causing mutation X253R increases betaB1-crystallin hydrophobicity to promote aggregate formation. Biochem J 473:2087–2096. [DOI] [PubMed] [Google Scholar]
  51. Lin H, Ouyang H, Zhu J, et al. 2016. Lens regeneration using endogenous stem cells with gain of visual function. Nature 531:323–328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Lin H, Yang Y, Chen J, et al. 2014. Congenital cataract: prevalence and surgery age at Zhongshan Ophthalmic Center (ZOC). PLoS One 9:e101781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Liu H, Liu H, Tang J, et al. 2017. Whole exome sequencing identifies a novel mutation in the PITX3 gene, causing autosomal dominant congenital cataracts in a Chinese family. Ann Clin Lab Sci 47:92–95. [PubMed] [Google Scholar]
  54. Liu L, Li K, Fu X, et al. 2016. A forward look at noninvasive prenatal testing. Trends Mol Med 22:958–968. [DOI] [PubMed] [Google Scholar]
  55. Lo WK, Biswas SK, Brako L, et al. 2014. Aquaporin-0 targets interlocking domains to control the integrity and transparency of the eye lens. Invest Ophthalmol Vis Sci 55:1202–1212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Lueder GT. 2006. Clinical ocular abnormalities in infants with trisomy 13. Am J Ophthalmol 141:1057–1060. [DOI] [PubMed] [Google Scholar]
  57. Luo L, Lin H, Chen W, et al. 2013. In-the-bag intraocular lens placement via secondary capsulorhexis with radiofrequency diathermy in pediatric aphakic eyes. PLoS One 8:e62381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Ma AS, Grigg JR, Ho G, et al. 2016. Sporadic and familial congenital cataracts: mutational spectrum and new diagnoses using next-generation sequencing. Hum Mutat 37:371–384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Ma F, Wang Q, Wang L. 2012. Advances in the management of the surgical complications for congenital cataract. Front Med 6:360–365. [DOI] [PubMed] [Google Scholar]
  60. Mackay D, Ionides A, Kibar Z, et al. 1999. Connexin46 mutations in autosomal dominant congenital cataract. Am J Hum Genet 64:1357–1364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Maher GJ, Black GC, Manson FD. 2012. Focus on molecules: lens intrinsic membrane protein (LIM2/MP20). Exp Eye Res 103:115–116. [DOI] [PubMed] [Google Scholar]
  62. Mansoor N, Mansoor T, Ahmed M. 2016. Eye pathologies in neonates. Int J Ophthalmol 9:1832–1838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Masters OW, Bergmans E, Thies KC. 2017. Anaesthesia and orphan disease: a child with Congenital Cataract Facial Dysmorphism neuropathy (CCFDN) syndrome: a case report. Eur J Anaesthesiol 34:178–180. [DOI] [PubMed] [Google Scholar]
  64. Mathias RT, White TW, Gong X. 2010. Lens gap junctions in growth, differentiation, and homeostasis. Physiol Rev 90:179–206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Mc Loone E, Joyce N, Coyle P. 2016. TORCH testing in non-familial paediatric cataract. Eye (Lond) 30:1275–1276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. McAvoy JW. 1978. Cell division, cell elongation and distribution of α-, β- and γ-crystallins in the rat lens. J Embryol Exp Morphol 44:149–165. [PubMed] [Google Scholar]
  67. McAvoy JW, Chamberlain CG, de Longh RU, et al. 1999. Lens development. Eye (Lond) 13:425–437. [DOI] [PubMed] [Google Scholar]
  68. Meinel UR. 1991. Practical cataract classification for epidemiological studies. Dev Ophthalmol 21:103–107. [DOI] [PubMed] [Google Scholar]
  69. Mochizuki T, Masai I. 2014. The lens equator: A platform for molecular machinery that regulates the switch from cell proliferation to differentiation in the vertebrate lens. Dev Growth Differ 56:387–401. [DOI] [PubMed] [Google Scholar]
  70. Morikawa S, Tajima T, Nakamura A, et al. 2017. A novel heterozygous mutation of the WFS1 gene leading to constitutive endoplasmic reticulum stress is the cause of Wolfram syndrome. Pediatr Diabetes [Epub ahead of print]. [DOI] [PubMed] [Google Scholar]
  71. Muller M, Bhattacharya SS, Moore T, et al. 2009. Dominant cataract formation in association with a vimentin assembly disrupting mutation. Hum Mol Genet 18:1052–1057. [DOI] [PubMed] [Google Scholar]
  72. Musleh M, Ashworth J, Black G, Hall G. 2016. Improving diagnosis for congenital cataract by introducing NGS genetic testing. BMJ Qual Improv Rep 5. pii: u211094.w4602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Mutti DO, Mitchell GL, Jones LA, et al. 2005. Axial growth and changes in lenticular and corneal power during emmetropization in infants. Invest Ophthalmol Vis Sci 46:3074–3080. [DOI] [PubMed] [Google Scholar]
  74. Nagamoto T, Oshika T, Fujikado T, et al. 2015. A survey of the surgical treatment of congenital and developmental cataracts in Japan. Jpn J Ophthalmol 59:203–208. [DOI] [PubMed] [Google Scholar]
  75. Park JE, Son AI, Hua R, et al. 2012. Human cataract mutations in EPHA2 SAM domain alter receptor stability and function. PLoS One 7:e36564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Pasyanthi B, Mendonca T, Sachdeva V, Kekunnaya R. 2016. Ophthalmologic manifestations of Hallermann-Streiff-Francois syndrome: report of four cases. Eye (Lond) 30:1268–1271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Pe’er J, Braun JT. 1986. Ocular pathology in trisomy 18 (Edwards’ syndrome). Ophthalmologica 192:176–178. [DOI] [PubMed] [Google Scholar]
  78. Pennie FC, Wood ICJ, Olsen C, et al. 2001. A longitudinal study of the biometric and refractive changes in full-term infants during the first year of life. Vis Res 41:2799–2810. [DOI] [PubMed] [Google Scholar]
  79. Perucho-Martinez S, De-la-Cruz-Bertolo J, Tejada-Palacios P. 2007. [Pediatric cataracts: epidemiology and diagnosis. Retrospective review of 79 cases]. Arch Soc Esp Oftalmol 82:37–42. [DOI] [PubMed] [Google Scholar]
  80. Prasov L, Masud T, Khaliq S, et al. 2012. ATOH7 mutations cause autosomal recessive persistent hyperplasia of the primary vitreous. Hum Mol Genet 21:3681–3694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Rahi JS, Dezateux C. 2000. Congenital and infantile cataract in the United Kingdom: underlying or associated factors. British Congenital Cataract Interest Group. Invest Ophthalmol Vis Sci 41:2108–2114. [PubMed] [Google Scholar]
  82. Rajappa M, Goyal A, Kaur J. 2010. Inherited metabolic disorders involving the eye: a clinico-biochemical perspective. Eye (Lond) 24:507–518. [DOI] [PubMed] [Google Scholar]
  83. Rajavi Z, Sabbaghi H. 2016. Congenital cataract screening. J Ophthalmi Vis Res 11:310–312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. Rees MI, Watts P, Fenton I, et al. 2000. Further evidence of autosomal dominant congenital zonular pulverulent cataracts linked to 13q11 (CZP3) and a novel mutation in connexin 46 (GJA3). Hum Genet 106:206–209. [DOI] [PubMed] [Google Scholar]
  85. Repka MX. 2016. Visual rehabilitation in pediatric aphakia. Dev Ophthalmol 57:49–68. [DOI] [PubMed] [Google Scholar]
  86. Santana A, Waiswo M. 2011. The genetic and molecular basis of congenital cataract. Arq Bras Oftalmol 74:136–142. [DOI] [PubMed] [Google Scholar]
  87. Sheeladevi S, Lawrenson JG, Fielder AR, Suttle CM. 2016. Global prevalence of childhood cataract: a systematic review. Eye (Lond) 30:1160–1169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  88. Shi Y, Barton K, De Maria A, et al. 2009. The stratified syncytium of the vertebrate lens. J Cell Sci 122:1607–1615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Shi Y, De Maria A, Bennett T, et al. 2012. A role for epha2 in cell migration and refractive organization of the ocular lens. Invest Ophthalmol Vis Sci 53:551–559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  90. Shiels A 2012. Focus on molecules: major intrinsic protein. Exp Eye Res 101:107–108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  91. Shiels A, Bennett TM, Hejtmancik JF. 2010. Cat-Map: putting cataract on the map. Mol Vis 16:2007–2015. [PMC free article] [PubMed] [Google Scholar]
  92. Shiels A, Hejtmancik JF. 2015. Molecular genetics of cataract. Progr Mol Biol Transl Sci 134:203–218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  93. Shore RE, Neriishi K, Nakashima E. 2010. Epidemiological studies of cataract risk at low to moderate radiation doses: (not) seeing is believing. Radiat Res 174:889–894. [DOI] [PubMed] [Google Scholar]
  94. Singh MP, Ram J, Kumar A, et al. 2016. Infectious agents in congenital cataract in a tertiary care referral center in North India. Diagn Microbiol Infect Dis 85:477–481. [DOI] [PubMed] [Google Scholar]
  95. Sminia ML, de Faber JTHN, Doelwijt DJ, et al. 2010. Axial eye length growth and final refractive outcome after unilateral paediatric cataract surgery. Br J Ophthalmol 94:547–550. [DOI] [PubMed] [Google Scholar]
  96. Somasundaram T, Bhat SP. 2004. Developmentally dictated expression of heat shock factors: exclusive expression of HSF4 in the postnatal lens and its specific interaction with alphaB-crystallin heat shock promoter. J Biol Chem 279:44497–44503. [DOI] [PubMed] [Google Scholar]
  97. Song S, Landsbury A, Dahm R, et al. 2009. Functions of the intermediate filament cytoskeleton in the eye lens. J Clin Invest 119:1837–1848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  98. Steinkellner H, Etzler J, Gogoll L, et al. 2015. Identification and molecular characterisation of a homozygous missense mutation in the ADAMTS10 gene in a patient with Weill-Marchesani syndrome. Eur J Hum Genet 23:1186–1191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  99. Sukonpan K, Phupong V. 2009. A biometric study of the fetal orbit and lens in normal pregnancies. J Clin Ultrasound 37:69–74. [DOI] [PubMed] [Google Scholar]
  100. Sureshkumar J, Haripriya A, Muthukkaruppan V, et al. 2012. Cytoskeletal drugs prevent posterior capsular opacification in human lens capsule in vitro. Graefes Arch Clin Exp Ophthalmol 250:507–514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  101. Tadros D, Trivedi RH, Wilson ME. 2016. Primary versus secondary IOL implantation following removal of infantile unilateral congenital cataract: outcomes after at least 5 years. J AAPOS 20:25–29. [DOI] [PubMed] [Google Scholar]
  102. Taylor VL, al-Ghoul KJ, Lane CW, et al. 1996. Morphology of the normal human lens. Invest Ophthalmol Vis Sci 37:1396–1410. [PubMed] [Google Scholar]
  103. Tian Q, Li Y, Kousar R, et al. 2017. A novel NHS mutation causes Nance-Horan Syndrome in a Chinese family. BMC Med Genet 18:2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  104. Trivedi RH, Wilson ME. 2007. Biometry data from caucasian and African-American cataractous pediatric eyes. Invest Ophthalmol Vis Sci 48:4671–4678. [DOI] [PubMed] [Google Scholar]
  105. Vasavada AR, Praveen MR, Tassignon MJ, et al. 2011. Posterior capsule management in congenital cataract surgery. J Cataract Refract Surg 37:173–193. [DOI] [PubMed] [Google Scholar]
  106. Vasavada AR, Vasavada V. 2017. Current Status of IOL implantation in pediatric eyes: an update. Expert Rev Med Devices :1–9. [DOI] [PubMed] [Google Scholar]
  107. Velasco-Annis C, Gholipour A, Afacan O, et al. 2015. Normative biometrics for fetal ocular growth using volumetric MRI reconstruction. Prenat Diagn 35:400–408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  108. Wang M, Xiao M. 2015. Congenital cataract: progress in surgical treatment and postoperative recovery of visual function. Eye Sci 30:38–47. [PubMed] [Google Scholar]
  109. Whitman MC, Vanderveen DK. 2014. Complications of pediatric cataract surgery. Semin Ophthalmol 29:414–420. [DOI] [PubMed] [Google Scholar]
  110. Willekens B, Vrensen G. 1982. The three-dimensional organization of lens fibers in the rhesus monkey. Graefes Arch Clin Exp Ophthalmol 219:112–120. [DOI] [PubMed] [Google Scholar]
  111. Wilson ME Jr, Trivedi RH, Buckley EG, et al. 2007. ASCRS white paper. Hydrophobic acrylic intraocular lenses in children. J Cataract Refract Surg 33:1966–1973. [DOI] [PubMed] [Google Scholar]
  112. Wilson ME, Trivedi RH. 2012. Axial length measurement techniques in pediatric eyes with cataract. Saudi J Ophthalmol 26:13–17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  113. Wirth MG, Russell-Eggitt IM, Craig JE, et al. 2002. Aetiology of congenital and paediatric cataract in an Australian population. Br J Ophthalmol 86:782–786. [DOI] [PMC free article] [PubMed] [Google Scholar]
  114. Wu X, Long E, Lin H, Liu Y. 2016. Prevalence and epidemiological characteristics of congenital cataract: a systematic review and meta-analysis. Sci Rep 6:28564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  115. Yao K, Wang W, Zhu Y, et al. 2011. A novel GJA3 mutation associated with congenital nuclear pulverulent and posterior polar cataract in a Chinese family. Hum Mutat 32:1367–1370. [DOI] [PubMed] [Google Scholar]
  116. Yu Y, Wu M, Chen X, et al. 2016. Identification and functional analysis of two novel connexin 50 mutations associated with autosome dominant congenital cataracts. Sci Rep 6:26551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  117. Yuan L, Yi J, Lin Q, et al. 2016. Identification of a PRX variant in a Chinese family with congenital cataract by exome sequencing. QJM 109:731–735. [DOI] [PubMed] [Google Scholar]
  118. Zhang R, Linpeng S, Wei X, et al. 2017. Novel variants in PAX6 gene caused congenital aniridia in two Chinese families. Eye (Lond) [Epub ahead of print]. [DOI] [PMC free article] [PubMed] [Google Scholar]
  119. Zhang X, Zhang Q, Tong Y, et al. 2011. Large novel deletions detected in Chinese families with aniridia: correlation between genotype and phenotype. Mol Vis 17:548–557. [PMC free article] [PubMed] [Google Scholar]
  120. Zhu Y, Yu H, Wang W, et al. 2014. A novel GJA8 mutation (p.V44A) causing autosomal dominant congenital cataract. PLoS One 9:e115406. [DOI] [PMC free article] [PubMed] [Google Scholar]

RESOURCES