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Congenital Clouding of the Cornea


Congenital clouding or opacification of the normally clear cornea can result from various genetic, metabolic, developmental, and idiopathic causes.

Early diagnosis is essential so that appropriate treatment can be initiated as early as possible and the child can obtain the best possible vision. Early ophthalmologic diagnosis can also facilitate recognition of an underlying systemic disorder.

A common reason for congenital clouding of the cornea is congenital glaucoma.

Other major causes of corneal clouding include the following:

Birth trauma

Peters anomaly

Dermoid tumors (limbal dermoids)


Congenital hereditary endothelial dystrophy (CHED)


Infectious/inflammatory processes

The following is a frequently used mnemonic for the causes of congenital clouding of the cornea:

S – Sclerocornea

T – Tears in the Descemet membrane secondary to birth trauma or congenital glaucoma

U – Ulcers

M – Metabolic

P – Peters anomaly

E – Edema (CHED)

D – Dermoid

Other rarer causes of congenital clouding or opacity of the cornea include the following: corneal keloids, congenital corneal ectasia, congenital hereditary stromal dystrophy, posterior polymorphous dystrophy, and Fryns syndrome.

Causes of congenital corneal opacities may be classified as primary corneal disease or secondary corneal disease. Primary corneal disease is developmental and may be isolated to the cornea or have a related systemic component. Secondary corneal disease may be developmental or acquired from metabolic diseases, trauma, or infections.


Sclerocornea is a congenital disorder of the anterior segment in which the cornea is opaque and resembles the sclera; the limbus is indistinct. Sclerocornea manifests as a nonprogressive noninflammatory congenital anomaly. It is usually seen as an isolated ocular abnormality involving both eyes, although it can occur unilaterally. This condition typically occurs sporadically but may also have a familial or autosomal dominant inheritance pattern.

On clinical evaluation, patients with partial sclerocornea have a peripheral, white, vascularized, 1- to 2-mm corneal rim that blends with the sclera, obliterating the limbus. The central cornea is generally normal. In total sclerocornea, the entire cornea is involved, but the center of the cornea is clearer than the periphery. This finding distinguishes it from Peters anomaly, in which the center is most opaque. The opacification affects the full thickness stroma and limits visualization of the posterior corneal surface and of the intraocular structures.

Histopathology reveals disorganized collagenous tissue containing fibrils that is larger than normal. Potential coexisting abnormalities include a shallow anterior chamber, abnormalities of the iris and the lens, and microphthalmos. Systemic abnormalities, such as limb deformities and craniofacial and genitourinary defects, can also accompany this finding. In generalized sclerocornea, early keratoplasty should be considered to provide vision, although the prognosis is guarded.

It has been argued that the term “sclerocornea” should be regarded only as a sign but not a diagnosis. Evaluation using ultrasound biomicroscopy (UBM) would better determine the presence of other anterior segment abnormalities such kerato-irido-lenticular adhesions.

Descemet membrane tears

Breaks in the Descemet membrane should be identified and differentiated from other abnormalities, such as the more vertically oriented defects seen after forceps-induced birth trauma or the irregularly scattered defects seen with posterior polymorphous dystrophy.

Forceps-induced obstetric trauma, with resultant Descemet membrane tears and corneal edema and clouding, is a cause of corneal clouding; it is almost always unilateral. This clouding is differentiated from primary congenital glaucoma (PCG) by the presence of periorbital soft tissue trauma, normal intraocular pressure (IOP), and the frequently vertical orientation of the Descemet membrane tears, and the absence of corneal enlargement, an abnormally deep anterior chamber, and an abnormal filtration angle.

Amniocentesis injury is extremely rare but should be considered in a patient with unilateral angular or linear opacity consistent with the appearance of a needle perforation. Lid damage and intraocular abnormalities such as cataract or iris or pupillary irregularity should raise suspicion.

Corneal edema and haze are common signs of congenital glaucoma, as are horizontal or circumferential breaks in the Descemet membrane (termed Haab striae). Haab striae will remain visible on examination throughout the patient’s life, even if the edema resolves with IOP normalization. Gonioscopic findings show a higher, flatter insertion of the iris at the level of the scleral spur, and the trabecular meshwork appears compacted.


Viral keratitis, such as herpetic keratitis or rubella keratitis, can result in a cloudy cornea in the newborn. Rubella keratitis in the newborn may particularly resemble PCG because it can be bilateral and associated with glaucoma. Infectious keratitis may also be caused by bacterial or fungal infection.

Metabolic causes


Mucopolysaccharidoses (MPS) can manifest with corneal clouding, including Hurler, Scheie, and Hurler-Scheie syndromes (all MPS I); Morquio syndrome (MPS IV); and Maroteaux-Lamy syndrome (MPS VI). Corneal clouding is not present in Hunter syndrome (MPS II) and Sanfilippo syndrome (MPS III).


For the most part, sphingolipidoses affect the retina, not the cornea, except in Fabry disease, an X-linked recessive disease. Fabry disease causes whorl-like opacities in the corneal epithelium (cornea verticillata), similar to those caused by chloroquine or amiodarone. Symptoms of Fabry disease also include skin lesions and peripheral neuropathy; renal failure is a common and serious complication.


Mucolipidoses manifest with corneal clouding, in particular GM gangliosidosis type 1 and mucolipidoses types I and III.

Peters anomaly

Peters anomaly is not an isolated anterior segment abnormality; rather, it occurs as a diverse, phenotypically heterogeneous condition associated with several underlying ocular and systemic defects.

Central, paracentral, or complete corneal opacity is always present in patients with Peters anomaly. Patients with type 1 Peters anomaly have iridocorneal adhesions, and the lens may or may not be cataractous; however, the lens does not adhere to the cornea. In type 2, the lens is cataractous and adheres to the cornea. Iridocorneal adhesions are often avascular, whereas keratolenticular adhesions are usually vascularized.

As with sclerocornea, the term “Peters anomaly” would be better regarded as a sign rather than a diagnosis, and ultrasound biomicroscopy evaluation should be performed for proper diagnosis and treatment planning.

Congenital hereditary endothelial dystrophy

Congenital hereditary endothelial dystrophy (CHED, formerly CHED2) is most likely only an autosomal-recessive disorder. The so-called autosomal-dominant–inherited CHED (formerly CHED1) is insufficiently distinct to continue to be considered a unique corneal dystrophy. On review of almost all published cases, the description appeared most similar to a type of posterior polymorphous corneal dystrophy linked to the same chromosome 20 locus (PPCD1).

CHED manifests in infancy as a nonprogressive cloudiness of the cornea, light sensitivity, tearing, and, in some cases, nystagmus. Infants with CHED are usually comfortable despite sometimes having profound corneal swelling. There is diffuse corneal edema, thickening of the Descemet membrane, and paucity of endothelial cells.

A large, Irish, consanguineous family with autosomal recessive CHED was examined to determine if the disease was linked to this region. The technique of linkage analysis with polymorphic microsatellite markers amplified by polymerase chain reaction (PCR) was used. In addition, a DNA-pooling approach to mapping of homozygosity was used to demonstrate the efficiency of this method. Conventional genetic analysis in addition to a pooled-DNA strategy excluded linkage of autosomal recessive CHED to the autosomal dominant CHED and large loci for posterior polymorphous dystrophy.

A clear association between congenital glaucoma and congenital hereditary endothelial dystrophy has been described in 3 patients. This combination should be suspected when persistent and total corneal opacification fails to resolve after bilaterally elevated IOP normalizes.

Harboyan syndrome

Harboyan syndrome manifests with diffuse bilateral corneal edema and occurs with severe corneal clouding, blurred vision, visual loss, and nystagmus. It is a congenital hereditary endothelial dystrophy (CHED) joined with progressive, postlingual sensorineural hearing loss.

According to Desir, 24 cases from 11 families of various origins (eg, Asian Indian, South American Indian, Sephardi Jewish, Brazilian Portuguese, Dutch, Gypsy, Moroccan, Dominican) have been reported.

Mutations in the SLC4A11 gene located at the CHED locus on band 20p13-p12 cause Harboyan syndrome, demonstrating that CHED and Harboyan syndrome are allelic disorders.

Corneal dermoids

Dermoids are benign congenital tumors that contain choristomatous tissue (tissue not normally found at that site). They most frequently appear at the inferior temporal quadrant of the corneal limbus. However, they are occasionally present entirely within the cornea or confined to the conjunctiva. They may contain a variety of histologically aberrant tissues, including epidermal appendages, connective tissue, skin, fat, sweat gland, lacrimal gland, muscle, teeth, cartilage, bone, vascular structures, and neurologic tissue (including brain tissue). Malignant degeneration is extremely rare.

The most common system for classifying dermoids is based on their location and separates the lesions into 3 broad categories. The most common dermoid is the limbal dermoid, in which the tumor straddles the limbus. These are usually superficial lesions, but they may involve deep ocular structures. The second type involves only the superficial cornea, sparing the limbus, the Descemet membrane, and the endothelium. The third type involves the entire anterior segment in which the cornea is replaced with a dermolipoma that may involve the iris, the ciliary body, and the lens. Ultrasound biomicroscopy can be helpful in determining the extent and depth of the lesion.

Inheritance is usually sporadic, although autosomal recessive or sex-linked pedigrees exist. They can be associated with corneal clouding.

Although most limbal dermoids are isolated findings, approximately 30% are associated with Goldenhar syndrome, especially when they are bilateral. Blepharoptosis, bilateral epibulbar dermoids, microphthalmia, epibulbar tumors, and retinal abnormalities have been documented in individuals with Goldenhar-Gorlin syndrome, also known as oculoauriculovertebral (OAV) dysplasia.

Dermoids may also be central and obstruct the visual axis.

The presence of corneal dermoid with an ipsilateral area of alopecia or nevus of the scalp should prompt MRI to evaluate for intracranial abnormalities and to diagnose encephalocraniocutaneous lipomatosis.

Corneal keloids

Perry noted, “Corneal keloids are hypertrophic scars of the cornea that may be present at birth following intra-uterine trauma but more often appear spontaneously or after minor trauma in early childhood.”
These scars seem to be related to an inappropriate repair response of the corneal tissue to trauma. They are also associated with Lowe syndrome.

Congenital corneal ectasia

Congenital corneal ectasia is an opaque, ectatic cornea extending between the lids and commonly occurring with corneal and lens clouding.

Congenital hereditary stromal dystrophy

Congenital hereditary stromal dystrophy manifests neonatally with a diffuse clouding of the central anterior corneal stroma with other normal corneal physical and nervous structures. The cornea is not edematous. It is nonprogressive. Its inheritance is autosomal dominant, and mutations in the decorin (DCN) gene have been implicated. Visual acuity is decreased. Strabismus and nystagmus may occur.

Posterior polymorphous dystrophy

Posterior polymorphous dystrophy (PPMD) is a slowly progressive, uncommon, dominantly inherited condition. It is usually bilateral but sometimes asymmetric. It manifests with isolated or coalescent posterior corneal vesicular (the most distinctive characteristic), multilayered Descemet membrane thickening, and a bandlike configuration with sharp scalloped margin. It can cause progressive corneal edema and is associated with iris irregularities and glaucoma. Bower has suggested that PPMD might be linked to Alport syndrome.
It rarely presents with corneal clouding at birth.

Fryns syndrome

First described in 1979, Fryns syndrome is a rare, generally lethal, autosomal recessive multiple congenital anomaly (MCA) syndrome. Patients with the syndrome present with the classical findings of cloudy cornea, brain malformations, diaphragmatic defects, and distal limb deformities.

Sanjad-Sakati syndrome

Sanjad-Sakati syndrome, also referred to as hypoparathyroidism-retardation-dysmorphism (HRD) syndrome, was reported as a cause of congenital clouding of the cornea in Oman.

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