Introduction
Developmental corneal anomalies are evident at birth, consequent to genetic, teratogenic, or idiopathic causes. During gestational week 5, as the lens vesicle separates from the surface ectoderm, the neural crest mesenchyme migrates between the surface ectoderm and the optic cup. The first wave of mesenchyme becomes the corneal endothelium and trabecular meshwork, the second becomes corneal keratocytes, and the third becomes the anterior iris stroma. Aberrations in this process result in the anomalies of corneal size, shape, and clarity, most commonly posterior polymorphous dystrophy, Peters’ anomaly, congenital glaucoma, and sclerocornea. Although pediatric keratoplasty is a challenging and complex procedure, recent series with a 40-month mean follow-up reported up to 78% graft success. However, medical therapy remains the predominant management (52.7%) of such eyes.
Size and Shape Anomalies
Microcornea
The normal horizontal corneal diameter is 9.5–10 mm at birth increasing to 10–12.5 mm by adulthood. An adult cornea that is less than 10 mm horizontally is considered microcornea and may occur in conjunction with microphthalmos, often associated with colobomas of the iris, retina, choroid, and even optic nerve ( Fig. 4.3.1 ). In contrast, nanophthalmos is a small functional eye that retains normal internal organization and proportion.
Epidemiology, Pathogenesis, and Ocular Manifestations
Most cases are sporadic, although autosomal recessive and autosomal dominant pedigrees have been reported. In microcornea, because the remainder of the eye is normal in size, lens development may cause angle-closure glaucoma. Microphthalmos in association with dermal aplasia and sclerocornea is termed MIDAS (microphthalmia, dermal aplasia, and sclerocornea) syndrome (caused by deletion in Xp22). An autosomal dominant variant of microcornea plus other anterior segment anomalies has been described. Microcornea also occurs in conjunction with numerous other anomalies, including the “micro-” syndrome of microcornea, congenital cataract, mental retardation, retinal dystrophy, optic atrophy, hypogenitalism, and microcephaly. It is also associated with fetal alcohol syndrome.
Treatment
Treatment involves spectacle correction for high hyperopia resulting from flat anterior corneal curvature. Other associations, such as cataract and glaucoma, are managed independently.
Megalocornea
Epidemiology, Pathogenesis, and Ocular Manifestations
Megaloconea with bilateral anterior segment enlargement is defined as horizontal corneal diameter of greater than 12 mm at birth or greater than 13 mm after age 2 years ( Fig. 4.3.2 ). Most commonly associated with mutations in the CHRDL (Xq23) gene, which encodes ventropin, defective growth of the optic cup is hypothesized to leave larger space for the development of the cornea. Congenital megalocornea with childhood secondary glaucoma from spherophakia and/or ectopia lentis is a distinct condition caused by recessive LTBP2 (14q24) mutations that must to be distinguished from buphthalmos—enlargement of the entire globe secondary to primary congenital/infantile glaucoma.
A number of variants have been described, and of those, the autosomal dominant form without other ocular abnormalities is the least common. X-linked recessive megalocornea is more frequent and is associated with iris transillumination, pigment dispersion, lens subluxation, arcus, and central crocodile shagreen. Endothelial cell density is normal, and this confirms that the enlargement does not arise from corneal stretching, and corneal clarity and thickness usually are normal. The genetic locus for X-linked megalocornea resides in the Xq21–q22.6 region. Megalocornea has been associated with congenital miosis, ectopia lentis, ectopia pupillae, mental retardation, congenital Marfan’s syndrome, albinism, and Neuhauser’s syndrome. Further distinction, however, is required from megalophthalmos, a probably autosomal recessive condition, comprising an enlarged cornea in an overall enlarged eye without glaucoma, also resulting in increased axial length (often >30 mm), juvenile cataract, and high myopia.
Treatment
Treatment is not necessary apart for spectacle correction for myopic refractive error and for somewhat challenging cataract surgery in a much enlarged anterior segment.
Corneal Absence
Developmental absence of the cornea does not occur in isolation, rather as a concomitant of severe dysgenesis of the anterior segment or the entire eye. Anophthalmos—total or subtotal absence of the entire eye—is consequent to, for example, extreme developmental disorders. Cryptophthalmos involves partial or complete failure of eyelid formation, corneal dermoids, and either a hypoplastic anterior segment or a rudimentary cyst-like globe with absence of anterior segment. Cryptophthalmos associated with systemic anomalies, such as syndactyly and genitourinary defects, is known as Fraser’s syndrome , an autosomal recessive trait. Pseudo-cryptophthalmos occurs when the lids fail to separate, but the underlying globe is intact.
Congenital Anterior Staphyloma
Keratoglobus (see Chapter 4.18 ) is not congenital, but a more extreme corneal ectasia may be present at birth as part of congenital anterior staphyloma, often also in concert with severe variants of Peters’ anomaly ( Fig. 4.3.3 ). This anomaly is usually unilateral and frequently also presents with iris developmental defects. Anterior staphyloma may occur consequent to inflammatory or infectious corneal thinning in utero.
Microcornea
The normal horizontal corneal diameter is 9.5–10 mm at birth increasing to 10–12.5 mm by adulthood. An adult cornea that is less than 10 mm horizontally is considered microcornea and may occur in conjunction with microphthalmos, often associated with colobomas of the iris, retina, choroid, and even optic nerve ( Fig. 4.3.1 ). In contrast, nanophthalmos is a small functional eye that retains normal internal organization and proportion.
Epidemiology, Pathogenesis, and Ocular Manifestations
Most cases are sporadic, although autosomal recessive and autosomal dominant pedigrees have been reported. In microcornea, because the remainder of the eye is normal in size, lens development may cause angle-closure glaucoma. Microphthalmos in association with dermal aplasia and sclerocornea is termed MIDAS (microphthalmia, dermal aplasia, and sclerocornea) syndrome (caused by deletion in Xp22). An autosomal dominant variant of microcornea plus other anterior segment anomalies has been described. Microcornea also occurs in conjunction with numerous other anomalies, including the “micro-” syndrome of microcornea, congenital cataract, mental retardation, retinal dystrophy, optic atrophy, hypogenitalism, and microcephaly. It is also associated with fetal alcohol syndrome.
Treatment
Treatment involves spectacle correction for high hyperopia resulting from flat anterior corneal curvature. Other associations, such as cataract and glaucoma, are managed independently.
Epidemiology, Pathogenesis, and Ocular Manifestations
Most cases are sporadic, although autosomal recessive and autosomal dominant pedigrees have been reported. In microcornea, because the remainder of the eye is normal in size, lens development may cause angle-closure glaucoma. Microphthalmos in association with dermal aplasia and sclerocornea is termed MIDAS (microphthalmia, dermal aplasia, and sclerocornea) syndrome (caused by deletion in Xp22). An autosomal dominant variant of microcornea plus other anterior segment anomalies has been described. Microcornea also occurs in conjunction with numerous other anomalies, including the “micro-” syndrome of microcornea, congenital cataract, mental retardation, retinal dystrophy, optic atrophy, hypogenitalism, and microcephaly. It is also associated with fetal alcohol syndrome.
Megalocornea
Epidemiology, Pathogenesis, and Ocular Manifestations
Megaloconea with bilateral anterior segment enlargement is defined as horizontal corneal diameter of greater than 12 mm at birth or greater than 13 mm after age 2 years ( Fig. 4.3.2 ). Most commonly associated with mutations in the CHRDL (Xq23) gene, which encodes ventropin, defective growth of the optic cup is hypothesized to leave larger space for the development of the cornea. Congenital megalocornea with childhood secondary glaucoma from spherophakia and/or ectopia lentis is a distinct condition caused by recessive LTBP2 (14q24) mutations that must to be distinguished from buphthalmos—enlargement of the entire globe secondary to primary congenital/infantile glaucoma.
A number of variants have been described, and of those, the autosomal dominant form without other ocular abnormalities is the least common. X-linked recessive megalocornea is more frequent and is associated with iris transillumination, pigment dispersion, lens subluxation, arcus, and central crocodile shagreen. Endothelial cell density is normal, and this confirms that the enlargement does not arise from corneal stretching, and corneal clarity and thickness usually are normal. The genetic locus for X-linked megalocornea resides in the Xq21–q22.6 region. Megalocornea has been associated with congenital miosis, ectopia lentis, ectopia pupillae, mental retardation, congenital Marfan’s syndrome, albinism, and Neuhauser’s syndrome. Further distinction, however, is required from megalophthalmos, a probably autosomal recessive condition, comprising an enlarged cornea in an overall enlarged eye without glaucoma, also resulting in increased axial length (often >30 mm), juvenile cataract, and high myopia.
Treatment
Treatment is not necessary apart for spectacle correction for myopic refractive error and for somewhat challenging cataract surgery in a much enlarged anterior segment.
Epidemiology, Pathogenesis, and Ocular Manifestations
Megaloconea with bilateral anterior segment enlargement is defined as horizontal corneal diameter of greater than 12 mm at birth or greater than 13 mm after age 2 years ( Fig. 4.3.2 ). Most commonly associated with mutations in the CHRDL (Xq23) gene, which encodes ventropin, defective growth of the optic cup is hypothesized to leave larger space for the development of the cornea. Congenital megalocornea with childhood secondary glaucoma from spherophakia and/or ectopia lentis is a distinct condition caused by recessive LTBP2 (14q24) mutations that must to be distinguished from buphthalmos—enlargement of the entire globe secondary to primary congenital/infantile glaucoma.
A number of variants have been described, and of those, the autosomal dominant form without other ocular abnormalities is the least common. X-linked recessive megalocornea is more frequent and is associated with iris transillumination, pigment dispersion, lens subluxation, arcus, and central crocodile shagreen. Endothelial cell density is normal, and this confirms that the enlargement does not arise from corneal stretching, and corneal clarity and thickness usually are normal. The genetic locus for X-linked megalocornea resides in the Xq21–q22.6 region. Megalocornea has been associated with congenital miosis, ectopia lentis, ectopia pupillae, mental retardation, congenital Marfan’s syndrome, albinism, and Neuhauser’s syndrome. Further distinction, however, is required from megalophthalmos, a probably autosomal recessive condition, comprising an enlarged cornea in an overall enlarged eye without glaucoma, also resulting in increased axial length (often >30 mm), juvenile cataract, and high myopia.
Corneal Absence
Developmental absence of the cornea does not occur in isolation, rather as a concomitant of severe dysgenesis of the anterior segment or the entire eye. Anophthalmos—total or subtotal absence of the entire eye—is consequent to, for example, extreme developmental disorders. Cryptophthalmos involves partial or complete failure of eyelid formation, corneal dermoids, and either a hypoplastic anterior segment or a rudimentary cyst-like globe with absence of anterior segment. Cryptophthalmos associated with systemic anomalies, such as syndactyly and genitourinary defects, is known as Fraser’s syndrome , an autosomal recessive trait. Pseudo-cryptophthalmos occurs when the lids fail to separate, but the underlying globe is intact.
Congenital Anterior Staphyloma
Keratoglobus (see Chapter 4.18 ) is not congenital, but a more extreme corneal ectasia may be present at birth as part of congenital anterior staphyloma, often also in concert with severe variants of Peters’ anomaly ( Fig. 4.3.3 ). This anomaly is usually unilateral and frequently also presents with iris developmental defects. Anterior staphyloma may occur consequent to inflammatory or infectious corneal thinning in utero.
Anomalies of Corneal Clarity
Depending on the affected wave(s) of neural crest mesenchyme migration, various corneal, angle and/or iris structures are compromised ( Table 4.3.1 ).
| Anomaly | Mesenchymal Wave Abnormality | ||
|---|---|---|---|
| 1st | 2nd | 3rd | |
| Posterior embryotoxon | x | ||
| Axenfeld–Rieger syndrome | x | x | |
| Peters’ anomaly | x | x | |
| Posterior keratoconus | x | ||
| Sclerocornea | x | ||
Anterior Embryotoxon
Anterior embryotoxon represents a congenitally apparent widening of the superior limbal transition from sclera to cornea. The term also describes arcus juvenilis, an appearance similar to arcus senilis but present at birth. Although often sporadic, autosomal dominant and autosomal recessive pedigrees have been described.
Posterior Embryotoxon
Posterior embryotoxon is highly prevalent, occurring in perhaps 24% of a random population. It comprises thickening and anterior displacement of Schwalbe’s line, most readily apparent in the temporal cornea ( Fig. 4.3.4 ). The term toxon , derived from the Greek word for “bow,” in reference to the crescent of Schwalbe’s line, when present alone has no functional significance.
Corneal Keloids
Keloids are white, glistening, protuberant lesions that involve all or part of the cornea. Although usually resulting from trauma or ocular inflammation, they may be evident at birth. Histopathologically comprising an irregular array of collagen, fibroblasts, and capillaries within the corneal stroma, they sometimes progress and may be associated with oculodigital disorders, such as Lowe’s syndrome. In otherwise healthy eyes, keratoplasty is appropriate. For lesions where growth causes discomfort, corneal dissection with a conjunctival flap may halt progression.
Dermoids
Dermoids are choristomas, defined as benign growths of tissue not normally present at a given location, and in the cornea they typically develop at the inferotemporal limbus where fusion of optic cup fissure occurs. At times they may involve larger areas of the cornea, the entire limbus, the entire cornea, or the interior of the eye. They usually are round, domed, pink to white to yellow in color and may have hair or, in the lipodermoid variant, globules of lipid. Depending on size, they constitute a minor cosmetic concern but may induce astigmatism or even consequent amblyopia, in which case surgical excision is indicated as also for larger lesions of anatomical and cosmetic concern. Limbal dermoids may be associated with other malformations, commonly Goldenhar’s syndrome, comprising lid colobomas, hemi-facial microsomia, preauricular skin tags, and other ear anomalies ( Fig. 4.3.5 ). Other mandibular and other facial anomalies may be concomitant and may be part of trisomy 8 mosaicism.
