Introduction

The treatment of corneal conditions in children can prove to be challenging. Not only are children at risk for infectious and inflammatory corneal conditions, but they can also have congenital conditions affecting the cornea and anterior segment. Recognizing these conditions is of the utmost importance because treatment can prevent corneal scarring and permanent visual loss. This chapter will be divided into several major subdivisions of congenital corneal opacification, developmental abnormalities, metabolic disease, and infectious etiologies.

Congenital corneal opacity

Embryology

To fully understand the origins of many of the congenital opacities of the cornea it is important to understand the embryogenesis of the anterior segment (meaning the cornea, anterior chamber, iris, and lens). The development of the cornea is triggered by the formation of the lens vesicle at about the sixth week of gestation.1 At this point the primitive corneal epithelium is resting on a thin acellular basement membrane, adjacent to which is the lens basement membrane and primitive lens vesicle. With separation of the lens vesicle, neural crest-derived mesenchymal cells migrate behind the epithelium forming the corneal endothelium. A second migration of neural crest cells occurs posterior to the forming endothelium, which is destined to form the iris. At the same time cells migrate between the epithelium and endothelium forming the keratocytes of the corneal stroma. By 3 months the endothelium thins to a single cell layer resting on its basal lamina, which is later called Descemet’s membrane.1 One of the more important concepts in the development of the cornea is that it is dependent on proper development of the lens.

ETIOLOGY

Peters anomaly was first desribed in 1906 by Peters2 and is the most common cause of congenital corneal opacity, accounting for approximately 40% of cases.3 It is an anomaly due to inadequate migration and differentiation of the neural crest cells in forming the anterior segment of the eye and is best classified as a neurocrestopathy.4,5

The exact etiology of Peters anomaly is not fully understood. The majority of cases are sporadic and in these cases teratogens such as prenatal rubella infection have been implicated.6 In cases where there is a family history of Peters anomaly, mutations in the genes FOXC1, PAX6, PITX2, FOXE3, and CYP1B1 have been implicated.7 Both autosomal dominant and recessive patterns of inheritance have been described.8 Most likely the findings in Peters anomaly are multifactoral in nature, arising from both genetic and environmental factors.

CLINICAL PRESENTATION

In Peters anomaly there is an area of corneal opacification with associated defects in the corneal stroma, Descemet’s membrane, and endothelium.9,10 In the majority of cases both eyes are involved.11 The opacity in the cornea may be quite subtle or encompass the entire cornea (86). It is also very common to see

86

86 8-week-old healthy boy born with anterior segment dysgenesis.Note the irregular cornea with scar tissue.The iris and lens are atrophic.

strands of iris tissue adherent to the margins of the corneal opacity. The lens may be clear or cataractous, and may be adherent to the posterior surface of the cornea. Many physicians will use the status of the lens to classify the anomaly into type I (no lens involvement) and type II (lens involvement).12

Peters anomaly can be associated with other ocular and nonocular findings. Glaucoma is a common finding in these patients. The proposed mechanism for the development of the glaucoma is inadequate formation of the pathway for aqueous drainage.13 Small eyes and retinal conditions have also been reported in association with Peters anomaly. Some of the nonocular conditions reported include developmental delay, congenital heart disease, external ear anormalies, central nervous system (CNS) abnormalities, genitourinary abnormalities, hearing loss, cleft lip and palate, and spinal defects. As most of the associated defects affect midline structures, the recommendation is to screen patients for heart and pituitary defects.14

MANAGEMENT/TREATMENT AND PROGNOSIS

Many children with Peters anomaly will require surgery to maintain vision. This is often corneal transplantation and glaucoma surgery to help keep the intraocular pressure under control. Major ophthalmic surgery in young children is quite challenging due to the severity of the disease.

Children with Peters anomaly require frequent follow-up. Often these examinations need to be performed under anesthesia. These frequent trips to the operating room can create both an emotional and financial burden for many families. Studies have shown the transplant survival rate to be between 40 and 60% at 3 years, and perhaps 50% of those

children will achieve a final vision of 20/200 or better.15,16

Sclerocornea

ETIOLOGY

Sclerocornea is a second congenital condition where the junction between the cornea and the adjacent sclera becomes indistinct. Sclerocornea tends to be a sporadic condition; however, as in most cases of anterior segment dysgenesis, both autosomal dominant and recessive patterns have been reported.17 In 1993 the MIDAS syndrome was introduced.18 This syndrome consists of microphthalmia, dermal aplasia, and sclerocornea and is due to deletion at Xp22.3. Typically in this syndrome there are skin defects that involve the upper body including the scalp, face, and neck. Nonocular findings include congenital heart defects, short stature, hypospadias, developmental delay, absence of the corpus callosum, nail dystrophy, and hydrocephalus.19 Though MIDAS syndrome has a defined area of chromosomal deletion, the exact genetic locus has not been identified.

CLINICAL PRESENTATION

The condition is nonprogressive and tends to be bilateral though often asymmetric.20 The opacification of the cornea may be peripheral or include the entire cornea, with fine blood vessels continuous with the surrounding conjunctiva. Sclerocornea can be seen as an isolated peripheral corneal opacity or it may be associated with other ocular and systemic abnormalities.10,21

MANAGEMENT/TREATMENT AND PROGNOSIS

As in Peters anomaly, many children will need corneal surgery for visual restoration. The destruction of the normal anatomy of the peripheral cornea reduces the success rate in corneal transplantation in sclerocornea. Preoperative ultrasound of the anterior segment (ultrasound biomicroscopy) to look for associated damage to the iris and angle has been helpful in surgical planning.22

Congenital dermoid

ETIOLOGY

Congenital dermoid tumors are limbal growths most commonly found in the inferonasal quadrant at the corneal limbus (87). They are typically composed of epidermal appendages but also may contain bone, cartilage, teeth, and even brain tissue. In the majority of patients corneal dermoids are an isolated finding. Systemic findings such as eyelid abnormalities and Goldenhar syndrome (88) have been reported with corneal dermoids.23,24 Any patient diagnosed with a dermoid tumor of the cornea should be closely examined for other associated eye, ear, and vertebral abnormalities. Though dermoids are generally thought to be spontaneous in nature, some familial transmission has been documented, where defects to Xq24-qter have been implicated.25 In other forms of dermoid tumors mutations to the gene PITX2 have been detected.26

CLINICAL PRESENTATION

The lesions appear clinically as smooth elevated masses most commonly crossing the corneal limbus in the inferonasal quadrant. Dermoid tumors rarely involve intraocular structures.24 Dermoids tend to be unilateral but bilateral cases have been reported.27

MANAGEMENT/TREATMENT AND PROGNOSIS

The treatment of corneal dermoids is based upon the threat to normal visual development and the concerns of the parents and the patient. Corneal dermoids may induce a unilateral astigmatism which can lead to amblyopia. Removal of the dermoid may be indicated as part of amblyopia treatment or to prevent its development. In some cases, the dermoid can be quite noticeable and becomes a social concern. Surgery can be performed in such cases. Surgery may consist of a partial keratectomy (removal of the anterior portion of the cornea) or a full thickness corneal graft, depending upon how deep the dermoid penetrates the cornea.

Birth trauma

ETIOLOGY

Severe corneal edema and opacity can result from birth trauma. The proposed mechanism of action in these cases is the blade of the forceps compresses the eye causing a rise in intraocular pressure and distention of the eye. These forces cause tears in Descemet’s membrane allowing swelling of the cornea.28 The injured and swollen cornea will often heal without surgical intervention but leaves vertical scars on Descemet’s membrane visible with a slit-lamp.

DIAGNOSIS

Diagnosis is made in a child with a history of birth trauma and findings consistent with that trauma. Other causes for corneal clouding need to be eliminated. As with any infant with corneal opacity, suspected birth trauma needs to be evaluated by an ophthalmologist.

MANAGEMENT/TREATMENT AND PROGNOSIS

In those patients who develop large levels of astigmatism, a contact lens can be used to create a more uniform corneal curvature. Even in these very young patients contact lens fitting can be performed and used to prevent permanent visual loss.29 Even if the cornea

remains clear, high astigmatism leading to amblyopia can be seen.30,31 Birth trauma can

lead to problems later in life. Late endothelial decompensation has been reported in patients with birth trauma after cataract surgery leading to corneal edema.32

Congenital hereditary endothelial dystrophy

ETIOLOGY

The congenital hereditary endothelial dystrophies (CHED) come in two forms, autosomal dominant (AD) and autosomal recessive (AR).33 The search for the genetic locus for CHED (both AD and AR) has led

89

89 Photo of an adult patient after having a transplant as a child for congenital hereditary endothelial dystrophy. Note the clear central corneal transplant and the cloudy peripheral cornea.

to chromosome 20.34,35 Studies using homozygosity mapping have shown that the genetic loci for the AD and AR forms of CHED are both on chromosome 20, but are distinct. These same studies have led to isolation of

the gene SLC4A11 on chromosome 20p in association with the AR form of CHED.36,37

With this new genetic information, testing and counseling may be beneficial to families in which a parent is affected and for sporadic cases of CHED.

CLINICAL PRESENTATION

In both AD and AR forms there are irregular endothelial cells and loss of cells. Descemet’s membrane shows fibrillar deposits in the posterior nonbanded zone. These changes allow hydropic swelling of the corneal stroma and epithelium, leading to increased thickness and a ground glass opacification.38 The AR form of CHED tends to present at birth with corneal opacification and nystagmus. The infants do not seem to have pain or light sensitivity. In contrast, the AD form of CHED presents at about 2 years of life with corneal swelling, light sensitivity and pain, but lacks the nystagmus.39 CHED tends to be isolated to the cornea and it is rare for it to be associated with other ocular or systemic conditions.

MANAGEMENT/TREATMENT AND PROGNOSIS

Unfortunately there is no medical treatment for endothelial diseases in children and adults alike. Children with either form of CHED have a poor visual prognosis if untreated and the majority of children will need corneal transplantation (89).38 Although the prognosis is still guarded, children with CHED seem to have a better prognosis then those with other causes of corneal opacity.40 The higher success may be related to the relative lack of associated damage to other structures of the eye.

Patients with a later onset of CHED (AD) seem to have a better prognosis than those presenting earlier in life.41 Early intervention is recommended to reduce the chances for amblyopia and permanently reduced vision.