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    Assessment

Tutorial
Introduction
Sclerocornea
Cornea Plana
Peters' Anomaly
Corneal Keloids
Corneal Dermoid
Goldenhar's Syndrome
Congenital Corneal Ectasia
Congenital Hereditary Stromal Dystrophy
Congenital Hereditary Endothelial Dystrophy
Posterior (Hereditary Deep Dystrophy) Polymorphous Dystrophy
References

Slides

Congenital Corneal Opacities

Henry D. Perry, MD · J. Douglas Cameron, MD

Introduction

Congenital corneal opacities are probably one of the most feared topics for ophthalmic residents and ophthalmologists. The occasion of a neonate with a congenital corneal opacity is a time of great concern in the neonatal nursery and one of catastrophic stress for the involved parents. Although a congenital corneal opacity is a rare occurrence, this difficult situation deserves study by any student of ophthalmology and must be mastered by corneal specialists. The perplexity of this topic is that genetic studies are only now identifying and classifying previous congenital leukomas in terms of true etiology. To ease understanding, we have chosen to discuss this group in terms of differential diagnosis at birth.

Sclerocornea

SLIDE 1

Sclerocornea is a totally opacified cornea that shows clinical and histologic features of sclera. The condition often is bilateral. Superficial or deep vascularization of the tissue may occur (Slide 1). Associated clinical conditions include nystagmus, strabismus, aniridia, cornea plana, macular aplasia, horizontally oval cornea, and glaucoma.¹ As described in Mieten's syndrome, patients with sclerocornea may present with congenital cerebral dysfunction, deafness, cryptorchidism, pulmonary disease, brachycephaly, and defects of the face, ears, and skin. Sclerocornea may be inherited in an autosomal dominant pattern. It also may be caused by intrauterine inflammation or other nonspecific causes.

Histologically, increased numbers of collagen fibrils with a variable collagen diameter occur in the normal corneal stroma. Descemet's membrane appears thin. Often the scleralization of the collagen fibrils stops in the pre-Descemet's region, permitting the performance of deep lamellar keratoplasties (Slide 2).

Cornea Plana

SLIDE 2

Cornea plana is an abnormal flattening of the curvature of the cornea. The cornea generally is normal in diameter. Cornea plana often is associated with sclerocornea and may be associated with microcornea, posterior embryotoxon, congenital cataract, iris and ciliary body coloboma, and macular aplasia. Diffuse deep stromal opacities may be present. The anterior chamber may be shallow, and the upper lid may appear ptotic. Astigmatism usually is present, although the eyes may be either myopic or hyperopic. The inheritance pattern is autosomal dominant or recessive linked to chromosome 12q21. Seventy-five percent of all sporadic cases occur in Finnish patients.²

The corneal tissue histologically is normal. The axial length of eyes that contain cornea plana is normal.³

Cornea plana is believed to result from an insult that occurs prior to the fourth month of gestation. After that time, corneal tissue develops a characteristic curvature independent of scleral curvature.⁴

Peters' Anomaly

SLIDE 3

Peters' anomaly includes absence of central corneal endothelium, Descemet's membrane, and variable amounts of corneal stroma (Slide 3). In most cases, Bowman's membrane also is absent. Peters' anomaly may be caused by primary dysgenesis of the corneal endothelial mesoderm, primary dysgenesis of keratocyte and endothelial neural crest mesoderm, or secondary endothelial degeneration due to late anterior displacement of a normally developed crystalline lens.⁵ In addition, it has been suggested that abnormal apposition of an ectopic lens to the developing cornea during the second or third month of gestation may be the cause of exceptional cases of peripheral Peters' anomaly (Slide 4).⁶

SLIDE 4

Associated anterior segment anomalies include corectopia, iris hypoplasia, anterior polar cataract or other lens abnormalities, and iridocorneal adhesion. Corneal perforations secondary to Peters' anomaly have been reported at birth.⁷ Systemic anomalies include Potter's syndrome (agenesis of the urinary tract).⁸ Generally, no specific inheritance pattern has been noted, although a family that had an autosomal dominant inheritance pattern has been reported.⁹

Histopathologic findings include absence of Descemet's membrane, corneal endothelium, and, usually, Bowman's membrane, as well as thinning of corneal stroma. The defects in Descemet's membrane, although usually single and central, may be multiple and isolated to the periphery, or they may be limited to an area of adhesion of iris.¹⁰ Descemet's membrane has been found to have embryonal ultrastructural characteristics combined with attenuated endothelium.¹¹ The corneal stromal lamellae are more irregular and closely packed when compared to normal stromal lamella.

Many forms of congenital leukoma have previously been lumped as Peters' anomaly only to have their true pathogenesis revealed by chromosomal studies. Immunohistochemical markers indicate that a normal complement of type I, III, IV, V, and VI collagen occurs in Peters' anomaly. However, an increased concentration of the adhesive protein fibronectin, which is known to play a role in the embryologic development of the cornea, may occur.¹²

Corneal Keloids

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. The opacity appears to be an inappropriate repair response of the corneal tissue to trauma. A sector of the cornea or the entire cornea may be involved. The inappropriate repair response usually coexists in the skin. Black people are most commonly affected. Recurrence is the rule, particularly following attempts at surgical excision.¹³ No inheritance pattern has been recognized.

The stromal nodules are composed of proliferating myofibroblasts, activated fibroblasts, and haphazardly arranged fascicles of collagen. Immunohistochemical stains show spindle cells that express immunoreactivity for vimentin and alpha smooth muscle actin.¹⁴ Keloid formation may be the result of excessive local delivery of amino acids and unknown noxious substances through leaking corneal vessels.¹⁵

Corneal Dermoid

Corneal dermoids are choristomas of mesenchymal elements covered by epithelium. The location and extent are variable. Corneal dermoids usually are sporadic, though autosomal recessive or sex-linked pedigrees have been described .¹⁶

SLIDE 5

The most common location is at the limbus, where the abnormal tissue is present in the peripheral cornea and in the adjacent episclera. Although the majority of limbal dermoids are isolated findings, approximately 30% are associated with Goldenhar's syndrome (see below). Although most limbal dermoids are superficial, the abnormal tissue occasionally extends into the anterior chamber angle tissue. Central corneal dermoids are the least common. The posterior cornea and Descemet's membrane are normal. On rare occasions, the entire cornea and anterior segment may be replaced by a dermoid. Descemet's membrane, iris, anterior chamber, and crystalline lens may be absent. This severe type often is associated with microphthalmos.¹⁷

Histologically, the corneal epithelium may be keratinized. Bowman's membrane often is absent. The stroma is replaced to a variable degree by irregularly arranged, dense, vascularized, collagenous connective tissue containing hair follicles, hair shafts, sebaceous glands, fat, smooth muscle, striated muscle, cartilage, teeth, or bone. The mass may be either cystic or solid.

Goldenhar's Syndrome

SLIDE 6

Goldenhar's syndrome consists of bilateral epibulbar dermoids, accessory auricular appendages, blind pretragal fistulas, and abnormalities of the cervical vertebrae¹⁸ (Slide 5 and Slide 6). The condition is important because of associated systemic abnormalities, including mandibulofacial dysostosis, phocomelia, and renal malformations. The first and second brachial clefts give rise to the ear, face, and eyelids. Goldenhar's syndrome is thought to result from a noxious insult during the seventh week of gestation, affecting the brachial clefts and a variable number of other germ tissues of other organ systems, primarily the kidney and skeleton. Associated brachial arch alterations include notching (so called coloboma) of the upper eyelid, antimongoloid slant of the palpebral fissures, microphthalmos, microcornea, uveal coloboma, hypoplastic upper and z lower jaw, micotia, and macrostomia. Nonbranchial arch alterations include anomalies of cervical vertebrae, heart disease, cleft palate, mental retardation, hydrocephalus, meningioencephalocele, phocomelia, renal hypoplasia, and partially annular pancreas.¹⁹

Congenital Corneal Ectasia

Congenital corneal ectasia is an opaque, ectatic cornea extending between the lids. If the ectactic cornea is lined by adherent iris, the condition is called corneal staphyloma. A patient with corneal staphyloma has a cornea with a blue hue caused by posterior approximation of atrophic iris tissue. Lens opacities are common. The posterior segment is normal. No inheritance pattern is evident. Congenital corneal ectasia is thought to be due to failure of migration of embryonic mesoderm to form corneal endothelium and iris stroma at approximately 7 weeks' gestation.²⁰

Histologically, the corneal epithelium has normal thickness but may be keratinized secondary to exposure. Often, local attenuation of Bowman's membrane occurs. The stroma is thickened, disorganized, hypercellular, and vascularized. A double layer of pigment-containing cells line the posterior corneal stroma. Usually, no sign of an inflammatory infiltrate is present. Descemet's membrane and corneal endothelium are absent.

Congenital Hereditary Stromal Dystrophy

SLIDE 7

This rare dystrophy consists of a diffuse haze of the central anterior corneal stroma. It is present at birth and nonprogressive. The remaining corneal structures, including corneal nerves, are normal. The condition is inherited in an autosomal dominant pattern. Vision is decreased and may be associated with strabismus and nystagmus.²¹ The basic defect appears to be disordered fibrogenesis of stromal collagen.

The collagen of the corneal stroma by electron microscopy consists of alternating layers of small-diameter collagen fibrils of approximately one-half the normal fibril diameter. Also, the anterior banded portion of Descemet's membrane is poorly developed. The endothelium is normal.

Congenital Hereditary Endothelial Dystrophy

SLIDE 8

Congenital hereditary endothelial dystrophy is a bilateral, stationary, diffuse opacification of ground glass density (Slide 7). Two modes of inheritance have been reported: an autosomal recessive type and a rarer, autosomal dominant type. In the autosomal recessive type, corneal clouding is present at birth or within the neonatal period. In the autosomal dominant type, the cornea generally is clear early in life. Corneal opacification develops slowly and progressively.²²

Histologically, increased diameter of stromal collagen fibrils may produce a thick cornea. Descemet's membrane is thickened in a manner similar to that found with Fuchs' endothelial dystrophy, implying a corneal endothelial abnormality.

Posterior (Hereditary Deep Dystrophy) Polymorphous Dystrophy

SLIDE 9

Posterior polymorphous dystrophy is a bilateral, autosomal, dominantly inherited disorder of the corneal endothelium. It is characterized by irregular, polymorphous opacities. Vesicles with central pigmentation and surrounding opacification are seen in the central cornea at the level of the endothelium and Descemet's membrane. The corneal opacities may vary greatly, even within the same family. Some individuals show only a few isolated vesicles while others manifest severe secondary stromal and epithelial edema. Still others show any stage in between.

SLIDE 10

Ruptures in Descemet's membrane may occur. In the more advanced cases, calcific and lipid degenerative changes occur in the stroma.²³ This dystrophy may present at birth as a diffuse clouding of the cornea. A number of patients have increased intraocular pressure.

Histologically, Descemet's membrane may be focally or diffusely thickened. Endothelial cells are multilayered and have desmosomes and intracytoplasmic filaments that are characteristic of epithelial cells. A layer of cells may be present beneath the corneal epithelium, but epithelial edema is not common. Iridocorneal adhesions, glassy membranes, and pupillary ectropion, which are changes found in the iridocorneal endothelial syndrome, also may be present in this condition.²³

Forceps injury to the cornea is usually an obvious diagnosis because there are frequently residual marks of the face and scalp. On occasion, these may be absent, and the cornea will be totally opaque and give rise to the consideration of acute glaucoma. However, the pressure and cornea size will be normal, and these corneas always clear within a few weeks. They can develop high degrees of astigmatism and are associated with the development of amblyopia in 50% of cases (Slide 8). Decades later, decompensation occurs and these cases are clinically thought of as unilateral Fuchs dystrophy (Slide 9). However, when the histology is performed on the surgical specimens, the finding of the characteristic breaks in Descemet's membrane will point to the correct etiology (Slide 10).²⁴ Last, another iatrogenic cause of corneal opacification is accidental corneal trauma from an amniocentesis.²⁵

References

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