History
A variety of historical scenarios are described for congenital clouding of the cornea. For example, a milky quality of the cornea may be noted at birth, with a decreased responsiveness to light. The obstetrician or the pediatrician may be the first to observe these ocular properties. The neonate may be completely asymptomatic, or he or she may have other ocular or systemic anomalies. The mother might give a history of prenatal exposure to a pathogen.
Maternal alcohol abuse
Three of 4 siblings born to parents with a history of heavy alcohol abuse had bilateral diffusely cloudy corneas at birth. The 3 siblings, who had mild systemic features of fetal alcohol syndrome (FAS), underwent corneal transplantations, and their specimens were examined under light and electron microscopy. On histology, alterations in the Bowman layer ranged from thickening to total loss. Various degrees of corneal stromal edema were observed. The unique pathologic feature in the corneas was the anomaly of the anterior banded zone of the Descemet membrane, which was absent, poorly formed, or thinned in the central and peripheral cornea. The corneal endothelium was attenuated or multilayered. The diffuse clouding and the range of histologic abnormalities in the corneas might have been related to the maternal alcohol abuse. [21]
Children with FAS may show a spectrum of eye abnormalities. External signs include short palpebral fissures, telecanthus, epicanthus, blepharoptosis, microphthalmos, and strabismus. Intraocularly, the most commonly detected signs include optic nerve hypoplasia and increased tortuosity of the retinal vessels. [22]
De Barsy syndrome
A male newborn had bilateral congenital corneal opacification. Examination revealed a variety of dysmorphic features, including cutis laxa, progeroid aspect, short stature, multiple hyperextensible subluxated joints, muscular hypotonia, and hyperreflexia. Bilateral penetrating keratoplasties were performed. Histopathologic examination revealed diffuse epithelial thickening, loss of the Bowman layer, and stromal attenuation with anterior stromal scarring. Special stains showed no deposition of abnormal material in the corneas. Electron microscopy demonstrated absence of the Bowman layer differentiation with a paucity of collagen fibers and extensive small, elastic fibers in the anterior stroma. The diagnosis was De Barsy syndrome, a rare, progeroid syndrome associated with characteristic ocular, facial, skeletal, dermatologic, and neurologic abnormalities.
De Barsy syndrome should be included in the differential diagnosis of congenital corneal opacification; its distinctive clinical features enable the clinician to easily differentiate it from other causes of congenital cloudy corneas. [23]
Congenital rubella
A cloudy cornea was observed in microphthalmic eyes in patients with congenital rubella. [24]
Clinical variant of Sanfilippo syndrome
A 4-month-old male infant had severe corneal opacity since birth. [25] Examination revealed buphthalmos, increased IOP, and corneal opacity with neovascularization but not a dysmorphic face or hirsutism. The liver and spleen were impalpable. Hypotonia, poor head control, and absence of Moro and grasping reflexes were noted. He had no evidence of congenital infection (toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex [TORCH] study). Urine and plasma amino acid levels were normal. However, thin-layer chromatography showed excessive urinary excretion of heparan sulfate. Corneal transplantation was performed at age 6 months. Histopathology of the corneal button showed homogeneous thickening of the Bowman layer and pinkish intracytoplasmic substances in the corneal stroma. The Alcian blue stain was positive, consistent with MPS of the cornea.
The manifestation in this case may be a clinical variant of Sanfilippo syndrome (MPS III).
Mucopolysaccharidoses
Mucopolysaccharidoses can result in corneal clouding but do not necessarily manifest in the natal period.
Physical
In infants with congenital corneal clouding, systemic and ocular findings that accompany the corneal opacity allow for the syndromic classification of the infant's condition.
Peters anomaly is an uncommon syndrome that manifests as central or paracentral corneal clouding. (See also Peters Anomaly.)
In type 1 Peters anomaly, 80% of cases are bilateral. Central or paracentral annular corneal opacity is present. The surrounding peripheral cornea may be clear or edematous because of glaucoma. The cornea is avascular. Iris strands often extend from the collarette, across the anterior chamber, to the posterior surface of the cornea. These strands may be filamentous or thick strands or sheets. A defect in the underlying corneal endothelium and the Descemet membrane causes the opacity. The lens may be clear or cataractous.
In type 2 Peters anomaly, cases are usually bilateral. The corneal opacity is dense and may be central or eccentric. The lens is usually cataractous and typically juxtaposed to the cornea. The posterior stroma, the Descemet membrane, and the endothelium are defective. Iris strands may or may not be present. Other ocular and systemic abnormalities are more common in type 2 than in type 1.
Corneal clouding, as observed by using a slit lamp, may be used in the differential diagnosis of mucopolysaccharidoses. Corneal clouding is present in MPS I, VI, and VII but absent in MPS II.
Causes
Causes of congenital corneal clouding are genetic, metabolic, developmental, infectious, and idiopathic.
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. Developmental causes are those that affect the cornea-iris-lens axis (kerato-irido-lenticular dysgenesis) or those that affect the iris-angle axis (iridotrabecular dysgenesis). Acquired causes include infection, trauma, and metabolic disorders.
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Congenital stromal dystrophy. The cornea is particularly opaque in the anterior stroma by slit-lamp biomicroscopy. Courtesy of Wikipedia (© 2009 Klintworth; licensee BioMed Central Ltd).
