A thorough history is the first step in evaluation of an infant with a corneal abnormality. This should include medical records for the child and a detailed obstetrical history. Any maternal exposure to drugs, toxins, or infectious agents during pregnancy, as well as any medications prescribed for the infant should be noted. It must also be determined if there is any family history of congenital disease.

There will be some instances in which an examination under anesthesia is required; however, this should be used as a last resort given the cost in added time and use of an operating suite. One useful method for an infant ocular examination is to instruct the parents to keep their child hungry before the visit. This will allow feeding to serve as a distraction and assist in keeping the child quiet during the examination. Another useful technique in maintaining comfort for the infant is to perform as much of the examination as possible with the child in the parent’s lap, having the parent handle and position the child when needed. Once calm and in position, instill topical anesthetic and place either a lid speculum or Koeppe lens to begin the examination (Fig. 1A). Instruments used in the evaluation of neonatal corneal abnormalities are listed in Table 1.

Portable slit lamp biomicroscopy is a useful technique for evaluation of the anterior segment (Fig. 1B). It is preferable to have a model with zoom optics and the capability of photography like the Kowa II portable slit lamp. This is optimal for obtaining good pictures and making the most accurate drawings of any abnormalities.³ Gonioscopy can then be performed with the Koeppe lens in place, but the lens must be removed for tonometry. If the cornea is heavily scarred or the globe is grossly distorted, then intraocular pressure must be estimated by palpation. After examination of the anterior segment, fundoscopy or other indicated studies (ERG, ultrasonography) can be performed. In some cases, severe corneal opacification will prevent visualization behind the cornea, and ultrasound biomicroscopy should be used to detect other anterior segment or vitreoretinal abnormalities.⁴ A complete infant ocular examination can be performed in approximately 2 hours.

Agenesis of the cornea is an extremely rare condition resulting from failure of the anterior segment to differentiate despite formation of the optic cup.⁵ The eye becomes completely surrounded by a scleral-like band of fibrous tissue. Absence of the cornea does not occur in isolation, rather it is always accompanied by the absence of other anterior segment structures such as the iris and ciliary body. Clinically, this condition can appear as a form of microphthalmos or apparent anophthalmos.

Cryptophthalmos is another relatively rare condition characterized by replacement of the eyelids with facial skin covering the orbit from the forehead to the cheek, connecting to the underlying globe and obliterating the cornea (Fig. 2A).⁶ This condition represents metaplastic change of the corneal epithelium and conjunctiva into stratified squamous keratinized epithelium.⁷ Cryptophthalmos can be unilateral or bilateral and usually occurs sporadically along with other congenital malformations including dyscephaly, syndactyly, and urogenital malformations. Although the pathogenesis is unclear, animal models suggest possible causes of cryptophthalmos syndrome to include defects in programmed cell death or vitamin A metabolism.⁸ An autosomal-recessive pattern of inheritance has been described for cryptophthalmos in as many as 25% of cases examined.⁹ Recent reviews have detailed the association of cryptophthalmos with other congenital malformations.^8,9

True (complete) cryptophthalmos, the most common form of this entity, is the result of failed formation of eyelid folds such that lashes and eyebrows are absent. In addition, lacrimal glands and canaliculi are generally absent. Although palpable, the underlying globe is microphthalmic with anterior chamber malformations. B-scan ultrasonography shows in a majority of cases the replacement of the remainder of the cornea and anterior chamber with connective tissue. Partial cryptophthalmos involves only the medial aspect of the eyelid, leaving the lateral eyelid normal in structure and function. Another form is abortive cryptophthalmos, or congenital symblepharon, in which only the upper eyelid undergoes metaplasia and remains adherent to the upper third of the cornea.¹⁰

Histopathologically, the skin consists of stratified squamous keratinized epithelium and an underlying dermis without appendages, which is fused to the fibrovascular tissue replacing the cornea. The anterior chamber is small or nonexistent, and the trabecular meshwork, Schlemm’s canal, iris, and lens are absent.¹¹ Surgical correction has been attempted for both complete and partial cryptophthalmos. The major goals of surgical intervention are to achieve a cosmetic improvement, to preserve the globe, and to protect any remnant of the cornea from infection (Fig. 2B).¹² There has been some success in restoring good visual function in patients with partial cryptophthalmos; however, this is not the true for cases of complete cryptophthalmos.¹²

The horizontal diameter of the newborn cornea is usually 10 mm, reaching the normal adult size of 11.8 mm by 2 years of age.¹³ Megalocornea is a congenital condition defined by a horizontal corneal diameter of greater than 12 mm in the newborn or greater than 13 mm in an adult without an associated elevation in intraocular pressure.¹⁴ Most often this is a nonprogressive bilateral symmetric corneal enlargement. There are three basic patterns of megalocornea (Table 2):

A-scan ultrasonography can be used to distinguish simple megalocornea from anterior megalophthalmos and buphthalmos. Only the anterior chamber will be enlarged in anterior megalophthalmos, whereas the entire globe will be enlarged in buphthalmos. Keratoglobus is a condition in which there is generalized thinning of the cornea, which may appear to be enlarged clinically but is usually normal in diameter.

Microcornea is defined by a horizontal corneal diameter of less than 11 mm.¹⁴ In this condition, the corneal diameter is usually between 7 and 10 mm, with some being reported as small as 4 mm.⁴¹ Accurate determination of the corneal diameter may be complicated in some cases by scleralization of the corneal limbus. The cornea is usually clear with normal thickness, and its shortened diameter usually creates a steep curvature with an increased refractive power. Instances of a flattened cornea with keratometry readings of less than 35 diopters have been reported in severe microcornea⁴² or in microcornea with sclerocornea.⁴³

The wide variety of ocular and systemic abnormalities that accompany microcornea make generalizations about this condition difficult. Associated ocular features can include other anterior segment malformations, such as sclerocornea or aniridia.⁴³ Microcornea can also present in cases of nanophthalmos, also called simple microphthalmos, in which the primary abnormality is a total reduction in the size of the globe.⁴⁴ Microcornea may also occur with congenital microphthalmos, in which there are multiple ocular abnormalities in conjunction with a small globe (Fig. 5).⁴⁵ Isolated cases of microcornea have also been reported.⁴⁶ Microcornea can be a sporadic condition, or it can be inherited in either autosomal dominant or autosomal-recessive patterns.⁴⁷

Assessment with A-scan ultrasonography is an important study in all patients with microcornea to establish if it is the cornea alone, or if the entire globe is small. Transillumination of the ciliary ring may help provide an accurate measurement of the true corneal diameter in cases with scleralization of the limbus. This will help distinguish microcornea from sclerocornea or cornea plana, in which an indistinct limbus produces the clinical appearance of a small cornea.

One histopathologic study of microcornea demonstrated a transformation of deeper corneal layers into scleral tissue at the true limbus.⁴⁸ The scleral spur and Schlemm’s canal were absent, with thinning and atrophy of the ciliary muscle. No changes were found in Descemet’s membrane.

Management of microcornea must include careful examination looking for other ocular conditions. Cataract must be ruled out because one presentation is the microcornea–cataract syndrome.⁴³ Routine examinations must also include intraocular pressure measurements to rule out glaucoma, which can occur in up to 20% of all cases.⁴⁹ In isolated microcornea, which can present as either myopia or hyperopia, correction of refractive error can provide an improved visual outcome.

An infant with a corneal opacification presents a diagnostic challenge for any ophthalmologist. A useful acronym to aid in recalling the differential diagnosis is STUMPED (Table 3). This mnemonic will hopefully prevent an ophthalmologist from becoming stumped when facing these conditions. The incidence of the different types of neonatal corneal opacities is unknown, but Peters anomaly and infantile glaucoma are the most common.

Sclerocornea is a condition in which normal cornea is replaced by white, vascularized tissue resembling the sclera, obliterating the limbus and scleral sulcus, and leaving a clearer central cornea (Fig. 6). This nonprogressive congenital anomaly is thought to result from defective mesenchymal migration at an early stage of differentiation.⁵⁰ Given the broad use of the term sclerocornea in a wide variety of corneal disease, it is not considered a distinct diagnostic entity.⁵¹

Both sexes are affected by sclerocornea and a majority of cases have bilateral involvement, which may be asymmetric. Half of all cases are sporadic, with the rest having either dominant or recessive patterns of inheritance,^51,52 with recessive forms usually more severe than dominant forms.⁵³ A number of ocular and systemic abnormalities are associated with sclerocornea, including skeletal and central nervous system abnormalities.⁵⁴ Chromosomal abnormalities may also occur.^53,55

Clinical presentation of sclerocornea can be quite varied. In some forms only a 1- to 2-mm rim of peripheral cornea is involved, leaving the central cornea clearer with distinct margins. More involved cases can include nodular extensions of scleral tissue into more central portions of the cornea. Sclerocornea can also present as a diffusely opaque cornea with peripheral vascularization or as a completely white and vascularized cornea. The fine, superficial vasculature appears to originate from the conjunctival vasculature.⁵¹ Either penlight or scleral scatter with the slit lamp best reveals the extent of sclerocornea. Diagnosis can be complicated in cases in which the entire cornea is involved and visualization of the anterior segment is limited. Ultrasound biomicroscopy is useful in assessing these corneas and establishing a diagnosis.⁵⁶

Sclerocornea is classified into four groups, although distinction among them is often imprecise: (1) isolated sclerocornea; (2) sclerocornea plana (cornea plana); (3) peripheral sclerocornea with anterior chamber cleavage abnormalities; and (4) total sclerocornea.

Tears or breaks in the endothelium and in Descemet’s membrane can be caused by either birth trauma or infantile glaucoma. Because the adult structure of the cornea is not reached until approximately 6 months of age,⁶⁴ the cornea of an infant is more elastic and prone to injury secondary to elevations in intraocular pressure. The elevated pressure produced either acutely by birth trauma or chronically in infantile glaucoma can distend the infant’s globe, exceeding the elasticity of Descemet’s membrane, resulting in tears. In either circumstance, the tears or breaks allow aqueous to enter the stroma and epithelium, producing corneal edema. The disparate clinical settings for birth trauma and infantile glaucoma should produce little confusion as to the cause of the tear.

Acute ocular birth trauma is being seen less often by ophthalmologists because of improved prenatal care and elective cesarian section reducing the rate of complicated forceps deliveries (Fig. 8A). Ocular trauma from forceps is thought to occur when the forceps blade slides over the inferior orbital rim, compressing the globe against the superior orbit and stretching the cornea horizontally.⁶⁵ Because the cornea is being compressed horizontally, these tears will line up in a vertical or oblique pattern (Fig. 8B). Other clinical findings associated with ocular birth trauma include ipsilateral periorbital edema and ecchymosis.

Corneal edema is the most common presenting sign of infantile glaucoma when it presents in the first 5 days of life, being present in 80% of cases.⁶⁶ By 6 months of age, approximately 75% of affected infants will manifest the corneal enlargement and buphthalmos characteristic of infantile glaucoma.⁶⁶ The tears in Descemet’s membrane caused by infantile glaucoma have a more random distribution, often circumferential to the limbus and sometimes extending sinuously toward the center of the cornea. Clinical features such as a delay in presentation of corneal edema, patterns of Descemet’s tears, and associated ocular findings help to clearly distinguish ocular birth trauma from infantile glaucoma.

When Descemet’s membrane tears, it retracts more in the center leaving a dehiscence with roughly parallel edges.⁶⁷ The stroma and epithelium overlying this tear will become diffusely edematous. Along the margin of the tear, Descemet’s membrane will often curl toward the stroma like a watch spring. Clinically, this curl forms a refractile edge evident under retroillumination through the corneal edema. It is important not to mistake these prominent edges for the tear itself, which is actually the space between these edges. To perform a complete anterior segment evaluation, it may be necessary to remove the edematous epithelium with a moist cotton swab. The corneal edema should resolve within weeks to months, provided the birth trauma was not too severe and that the intraocular pressure was surgically lowered in cases of infantile glaucoma.

With time, a fresh endothelium will resurface the posterior cornea and synthesize a new basement membrane, filling the dehiscence and accentuating the edges of the tear. After the corneal edema resolves, the edges of the break will appear as rounded, glassy ridges protruding from the posterior cornea readily apparent under retroillumination. In some instances, one edge of the tear may separate from the stroma and hang into the anterior chamber as a falciform ledge, with its free edge curling anterior to form a scroll (Fig. 9). When two tears occur parallel to each other, the edge of Descemet’s membrane between the tears may curl toward each other. This strip of Descemet’s may then disassociate from the overlying stroma, resulting in a glassy strand across the concavity of the posterior cornea. In this circumstance, the newly laid basement membrane will have a beaten-metal, guttate appearance.

Histopathologically, the edge of a Descemet tear curls toward the stroma, possibly because of the differential elasticity between the anterior banded and posterior nonbanded layers within Descemet’s membrane.⁶⁷ As the new regenerating endothelium spreads over the edge, it encases the original coiled Descemet’s membrane in a thick multilaminar periodic acid-Schiff (PAS)-positive basement membrane (Fig. 9). This new basement membrane forms the clinically evident refractile edge. Within the bed of the tear, the regenerating endothelium lays down an irregular basement membrane with focal excrescences that produce the beaten-metal appearance.

Ultrastructural studies of the cornea in human congenital glaucoma are rare,⁶⁸ but the ultrastructure in rabbits with spontaneous buphthalmos has been described in detail.⁶⁹ Intraepithelial and subepithelial edema is present, accounting for the ease with which one can remove the epithelium clinically. Stromal edema, loss of regular collagen architecture, and the degree of scarring correlate with the degree of corneal opacity and thickness. In rabbits with mild to moderate corneal clouding, Descemet’s membrane is thicker than normal and manifests the compact structure typical of basement membrane. In rabbits with more severe corneal opacification, a layer of small-diameter collagen fibrils enmeshed in amorphous material appears posterior to Descemet’s membrane. In these rabbits, no tears in Descemet’s membrane are observed clinically or histopathologically, suggesting that corneal edema may occur from elevated intraocular pressure alone. The thin endothelial cells can be as large as four times their normal size and contain cytoplasmic vacuoles appearing as small pits on scanning electron microscopy. In humans, these enlarged endothelial cells may represent the ones that decompensate later to produce corneal edema. Recently, in vivo confocal microscopy has been used to further evaluate Descemet’s tears and endothelial changes associated with congenital glaucoma.⁷⁰ Key findings include a mild reduction of keratocyte density in the middle and posterior stroma, along with the presence of discontinuous hyperreflective structures overhanging the endothelial layer at the level of Descemet’s membrane. Additional confocal analysis of the endothelial layer demonstrate a low cell count, focal cellular lesions, severe polymegethism, and pleomorphism.⁷⁰

Treatment is generally not necessary for patients with ocular forceps injury. The corneal edema will usually resolve within weeks. Corneal astigmatism may result from this injury and will require early refraction and patching to prevent amblypoia.⁶⁵ In some instances, the edema may persist and form an opacification, which may require penetrating keratoplasty. In this circumstance, the visual prognosis is poor in the affected eye. Young children with infantile glaucoma may require surgery to control intraocular pressure. Treatment of infantile glaucoma may result in a decrease in buphthalmos and a change in corneal diameter toward normal; however, some residual corneal edema may persist. Under these circumstances, early penetrating keratoplasty is indicated and can be successful.⁷¹ Decompensation of previously stressed endothelium from either infantile glaucoma or birth trauma can occur 20 to 30 years after the original insult, requiring penetrating keratoplasty to restore vision.⁷² In one study of endothelial decompensation related to infantile glaucoma, the overall success rate for penetrating keratoplasty was 75%; with adequate control of intraocular pressure being a key factor in preventing graft failure.⁷³

Another form of prenatal trauma that can produce corneal opacification is an amniotic band, which by stretching across the face during development may cause a cleft lip occasionally associated with microphthalmia and a hazy cornea. This corneal haze is likely the result of direct trauma to the cornea and not from tears in Descemet’s membrane.⁷⁴

Corneal ulcers are rarely present at birth, but when an epithelial defect does occur in a neonate, the differential diagnosis should include herpes simplex keratitis, bacterial keratitis, and neurotrophic keratitis.