Congenital Cataract

Congenital cataract is a cloudy or opaque area in the (normal crystal clear) lens of the eye or in the surrounding membranes of the lens present at birth.

ICD-10: Q12.0 Congenital cataract

Little is known about the incidence of fetal cataracts. The incidence of pediatric cataracts varies with socio-economic status, due to, for example, inadequate health-care systems and higher rates of perinatal infections in low-income countries (1-3). Incidences range from 1.8 to 13.6 per 10 000 births in high-income countries (4-7) to 5 to 15 per 10.000 births in low- to middle-income economies countries (1,2).  

There is no clear gender difference (4,5,8-10) with possibly a slight male dominance for bilateral cataract and female dominance for unilateral cataract (11,12).  

The occurrence of cataract in Down syndrome children has been reported to be as high as 50%. A large study from Haargaard however showed that the frequency of Down syndrome children actually born with cataract in Sweden and Denmark is much lower: about 1% (13). 

The first morphological indication of eye development is a bilateral out-pocketing of the neural ectoderm wall of the diencephalon in the 6^th week of gestation forming the  optical vesicle. The embryonic origin of the lens however is from surface ectoderm. The first stage of lens differentiation takes place when the optic vesicle, comes in proximity to the surface ectoderm. The ectoderm cells in contact with the optic vesicle begin to elongate and form the lens placode. As development progresses, the lens placode begins to invaginate. As the placode continues to deepen, the opening to the surface ectoderm constricts.  At 7 weeks gestational age, the lens placode has completely separated from the surface ectoderm and forms a lens vesicle (14). The embryonic nucleus, that will ultimately occupy the central area of the lens, is formed from cells in the posterior layer of the lens vesicle. Around this embryonic nucleus fibers from the anterior epithelium are deposited forming the fetal nucleus. Eventually the transparent, biconvex, avascular, semi solid lens is composed of 4 structures: capsule, epithelium, embryonic nucleus and fetal nucleus. Postnatal the infantile nucleus, adult nucleus and the cortex are formed as concentric layers; the youngest fibers as the most peripheral (15). All kinds of disruptions at different times during embryologic development may result in different phenotypes found in congenital cataract.

Most pediatric etiology studies show that next to idiopathic cataract, hereditary factors are the second most common causes of congenital cataract (10,11,16-19).  Cataracts can be part of several genetic conditions such as musculoskeletal conditions and many others (20,21). It has to be kept in mind that in pediatric studies the numbers of cataracts as part of lethal conditions are underestimated.

More than 100 genes related to cataract have been identified (21). One type of gene mutation can give a large variation in phenotype, with even important intrafamilial variability (21). Bilateral cataract is more often seen in hereditary conditions (22,23).  

Other causes of congenital cataracts are infections of which rubella is the most common. Other possible infections that may lead to cataract are toxoplasmosis, cytomegalovirus, herpes simplex, coxsackievirus, Ebstein-barr virus, varicella, syphilis, HIV, parvo B19, influenza and poliomyelitis. The embryo is particularly vulnerable for developing cataract especially before the 7^th seven week (when the lens vesicle is not yet separated from the ectoderm). Later in pregnancy fetal infections rarely lead to cataract (24). Congenital nonsyndromic cataract may also be the result of hyperthermia during organogenesis and antifever therapy may restrict the teratogenic risk of hyperthermia (25).

Other possible causes of congenital cataract are metabolic diseases (e.g. Zellweger syndrome, chondrodysplasia punctata), diabetes or drug reactions (e.g. coumarine derivates).

Older mothers (12) and a low birth weight (7,12) are associated with an increased risk of congenital cataract.

Normally, an image is focused on the retina, by refraction of light through the crystal clear lens. During the first months of life, the brain develops vision in response to a clear image. Cataract scatters the light and can obstruct the passage of light to the retina, which will interfere with normal visual system development, producing visual impairment. Small opacities in the anterior portion of the lens or in the periphery may have no negative impact on visual development.

A cataract can be unilateral, bilateral or asymmetrical (one eye is more affected then the other eye). A cataract can appear in any part of the lens and range in size from small dots to total opacity involving all the lens structures. Nuclear cataract (appearing in the central part of the lens) is the most common form of congenital cataracts. Other forms based on the anantomic location are anterior or posterior polar cataract, capsular cataract, subcapsular cataract or complete cataract. Some forms are insignificant for visual development or do not progress while others progress and may produce profound visual impairment.

A cataract may be accompanied by additional ocular abnormalities and systemic conditions (11). Microphthalmia is the most common associated ocular anomaly (26,27). Idiopathic unilateral cataract shows a relative high proportion of additional ocular abnormalities (11). Other associated ocular anomalies (mostly very difficult or impossible to visualize on prenatal ultrasound) are retinal detachment, colobomas,  microcornea, megalocornea, zonular dehiscence and persistent fetal vasculature (28) or anterior chamber defects, like aniridia (29,30). 

In nonsyndromic pediatric cataract other systems frequently involved are the central nervous system (for instance microcephaly or ventriculomegaly) followed by the respiratory system (19).

Syndromic cataract can be part of several genetic conditions such as musculoskeletal conditions like chondrodysplasia punctate (31,32), Lowe’s syndrome (33), Walker-Warburg syndrome (34,35,36), multiple pterygium syndrome (37,38) or cerebro-oculo-facio-skeletal syndrome (39,40). Other genetic conditions associated with cataract are Micro syndrome (23,27), Smith-Lemli-Opitz syndrome (41), trisomy 21 (42), Nance-Horan (43) and many others (20,21).  

More than 100 genes associated with cataracts are identified (21). Inheritance can be autosomal dominant (the most common), autosomal recessive or X-linked. The phenotype is variable, with significant inter-familial and intrafamilial variability.

The ultrasound image of cataract is variable and includes a homogenous opacity, thick hyper echogenic borders or irregular clusters of hyper echogenic spots (38,44).  Early diagnosis (from 14 weeks onwards) are reported with vaginal ultrasound (38,45,46).

The natural history and the time of onset varies among different conditions. Therefore, the demonstration of clear lenses especially early in pregnancy does not exclude congenital cataract. Both lenses have to be visualized as cataracts can affect one eye, both eyes or can be asymmetrical. Ultrasound may fail to detect moderate cataract (47). Normal values of lens diameter and circumference are available (48) and may sometimes be of help (36).

Differential diagnosis includes retinoblastoma, coloboma, vitreous hemorrhage and tumors.

Hyperechogenity in the anterior part of the eye can be seen in anterior segment dysgenesis (ASD), an abnormal development of the anterior segment of the eye including the cornea, iris and lens. Conditions associated with ASD are aniridia, Peters syndrome (29) and Axenfeld-Rieger anomaly (49).  

Persistent fetal vasculature is often associated with cataracts (28,50).

Sometimes the pupil (i.e. musculus sphincter pupillae) is visible as a thin vague circle. This should not be confused with cataract.

Since it was recognized that early surgery (within first months of life) is critical for a good visual prognosis, the visual outcome and quality of life is good for non-syndromic isolated cases (51,52).  

A serious complication that may occur following cataract surgery is glaucoma, especially when microcornea or persistens fetal vasculature is present (53). Other less common postoperative complications include posterior capsule opacification, lens reproliferation, pupillary membrane, amblyopia and rarely infections, bleeding, and retinal detachment. Long-term follow-up and frequent monitoring of the eye by an ophthalmologist will be necessary (54). Not all congenital cataract patients need surgery. Very small or peripheral cataracts may have no negative impact on visual development.

If serious congenital cataract goes undetected in a neonate, the visual prognosis is poor and permanent visual loss may ensue. Blurred or distorted vision will cause the brain to set up abnormal visual connections. This abnormal visual development is named amblyopia, which leads to other problems such as nystagmus and strabismus.

Associated anomalies and the kind and severity of an underlying condition have a major impact on the prognosis.

If a cataract is recognized on ultrasound examination, referral to a fetal medicine unit should take place. The anatomy of both eyes has to be scrutinized in detail as cataracts can be accompanied by additional ocular abnormalities and can be unilateral, bilateral or asymmetrical. All organ systems, but especially the central nervous system, require investigation.

Cataracts, especially when bilateral, are associated with several genetic conditions. Therefore, genetic consultation and testing is strongly recommended in addition to exclusion of infectious causes.

Family history may reveal hereditary forms of cataract and a careful history should be taken, including illnesses or medications used during pregnancy.

Obstetric care is dependent on the presence of associated or genetic anomalies. If these are not present, standard obstetric care can be applied. Otherwise, obstetric and delivery management should be changed accordingly. The cause of cataracts however may not become evident during pregnancy, therefore management of the pregnancy in a tertiary center should be considered.

As congenital cataract is an important preventable cause of visual impairment and blindness, the eyes of the neonate should be examined shortly after birth whenever there is any suspicion for cataract.

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