indicated, as optical correction and patching may be required. Trauma from amniocentesis is a rare cause of unilateral corneal opacification in a newborn.
Corneal ulcers Corneal ulcers that are present at or develop around birth are rare and may be caused by herpes simplex keratitis or other infection (bacterial) (see Chapter 28).
Treatment of Corneal Opacities
The treatment of congenital corneal opacities is difficult but can be rewarding as long as the clinician understands that the goals include both corneal graft clarity and improvement in visual function. If bilateral dense opacities are present, early keratoplasty should be considered for 1 eye so that deprivation amblyopia can be minimized. If the opacity is unilateral, the decision is more difficult. Keratoplasty should be undertaken only if the family and the ophthalmologists are prepared for the significant commitment of time and effort needed to deal with corneal graft rejection, which often occurs in children, as well as with amblyopia. The team should include ophthalmologists skilled in pediatric corneal surgery, pediatric glaucoma, and amblyopia. Contact lens expertise is important for infants with small eyes and large refractive errors. Repeated examinations under anesthesia are often required.
In addition to penetrating keratoplasty, treatment options include optical iridectomy, deep anterior lamellar keratoplasty (DALK; used for stromal disease with healthy endothelium), DSEK (used to replace diseased endothelium or Descemet membrane), and keratoprostheses.
Ashar JN, Ramappa M, Vaddavalli PK. Paired-eye comparison of Descemet’s stripping endothelial keratoplasty and penetrating keratoplasty in children with congenital hereditary endothelial dystrophy. Br J Ophthalmol. 2013;97(10):1247–1249. Epub 2013 Apr 23.
Harding SA, Nischal KK, Upponi-Patil A, Fowler DJ. Indications and outcomes of deep anterior lamellar keratoplasty in children. Ophthalmology. 2010;117(11):2191–2195.
Congenital and Developmental Anomalies of the Globe
Microphthalmos
Microphthalmos refers to a small, disorganized globe, often with an associated cystic outpouching of the posteroinferior sclera. It may be isolated or syndromic. Mutations of the CHX10, MAF, PAX6, PAX2, RAX, SHH, SIX3, and SOX2 genes have been reported in microphthalmos.
Anophthalmos
True anophthalmos (absence of any ocular globe tissue) is very rare and often extreme. Usually, severe microphthalmos is present, giving a clinical picture of anophthalmos. The genes involved in anophthalmos are the same as those involved in microphthalmos.
Nanophthalmos
Nanophthalmos refers to a small but normal eye. The patient has a high degree of hyperopia (+7–+10 D) due to the short eye. There is a high lens-to-eye ratio, leading to a shallow anterior chamber and angle-closure glaucoma.
Congenital and Developmental Anomalies of the Iris and
Pupil
Abnormalities of the Iris
Persistent pupillary membranes
Persistent pupillary membranes (Fig 20-7) are the most common developmental abnormality of the iris. They are present in approximately 95% of newborns, and remnants are common in older children and adults. Persistent pupillary membranes are rarely of any visual significance. However, if especially prominent, they can adhere to the anterior lens capsule, causing a small anterior polar cataract. They may also be associated with other anterior segment abnormalities.
Figure 20-7 Persistent pupillary membranes. Uncorrected visual acuity is 20/40.
Ramappa M, Murthy SI, Chaurasia S, et al. Lens-preserving excision of congenital hyperplastic pupillary membranes with clinicopathological correlation. J AAPOS. 2012;16(2):201–203.
Iris hypoplasia
When the iris stroma is underdeveloped, it is termed iris hypoplasia. When the posterior pigment epithelium is underdeveloped, it results in iris transillumination (discussed later). When the condition involves both structures, it may be focal (iris coloboma) or diffuse (aniridia).
Axenfeld-Rieger syndrome Axenfeld-Rieger syndrome is the commonest cause of iris (stromal) hypoplasia. This syndrome represents a spectrum of developmental disorders characterized by
posterior embryotoxon, with attached iris strands, iris hypoplasia, and a 50% lifetime risk of glaucoma (Figs 20-8, 20-9, 20-10). The conditions—previously called Axenfeld anomaly, Rieger anomaly or syndrome, iridogoniodysgenesis anomaly or syndrome, iris hypoplasia, and familial glaucoma iridogoniodysplasia—all overlap genotypically and phenotypically and are now considered a single entity known as Axenfeld-Rieger syndrome. With the identification of several causative genes and loci for these disorders, it is now known that the same ocular appearance can be caused by different genes, and very different ocular presentations can be caused by the same mutated gene. In the latter circumstances, the different ocular presentations previously would have been classified as distinct conditions—Peters anomaly, Rieger anomaly, or primary glaucoma, for example.
Axenfeld-Rieger syndrome may include a smooth, cryptless iris surface and a high iris insertion, sometimes accompanied by iris transillumination. Iris hypoplasia can range from mild stromal thinning to marked atrophy with hole formation, corectopia, and ectropion uveae. The severity of the iris hypoplasia may be so great as to mimic aniridia. Posterior embryotoxon, megalocornea (secondary to glaucoma), or microcornea may occur. Associated nonocular abnormalities include abnormal teeth, redundant periumbilical skin, hypospadias, and anomalies in the region of the pituitary gland.
Autosomal dominant inheritance is most common. Mutations in the PITX2 gene on band 4q25 have been identified. This is a paired homeobox gene that regulates expansion of other genes during embryonic development. Patients with mutations of PITX2 have been reported to have phenotypes of aniridia, Peters anomaly, and Axenfeld-Rieger syndrome. The nonocular findings are more consistent and should be sought with any of these ocular phenotypes. Mutations in the forkhead transcription factor gene FOXC1 (formerly called FKHL7) also cause Axenfeld-Rieger syndrome, generating features such as autosomal dominant iris hypoplasia, glaucoma, Axenfeld-Rieger syndrome, posterior embryotoxon, Peters anomaly, and primary congenital glaucoma. FOXC1 is also expressed in the heart, and some patients have cardiac valve abnormalities.
Figure 20-8 Gonioscopic view in Axenfeld-Rieger syndrome.
Figure 20-9 Axenfeld-Rieger syndrome, bilateral.
Figure 20-10 Axenfeld-Rieger syndrome. Note variation compared with Figures 20-2 and 20-9. (Courtesy of Jane D. Kivlin, MD.)
Iris transillumination In albinism, diffuse iris transillumination results from the absence of pigment in the posterior epithelial layers. Iris hypoplasia can also lead to iris transillumination, especially as part of Axenfeld-Rieger syndrome or iridocorneal endothelial (ICE) syndrome. In addition, iris transillumination may occur in Marfan syndrome, ectopia lentis et pupillae, X-linked megalocornea, and microcoria. Patchy areas of transillumination can also be seen after trauma, surgery, or uveitis. Scattered iris transillumination defects may be a normal variant in individuals with very lightly pigmented irides.
Coloboma of the iris Iris colobomas are classified as typical if they occur in the inferonasal quadrant and can thus be explained by failure of the embryonic fissure to close in the fifth week of gestation. With a typical iris coloboma, the pupil is shaped like a lightbulb, keyhole, or inverted teardrop (Fig 20-11). Typical colobomas may also involve the lens, ciliary body, choroid, retina, and optic nerve. These colobomas are part of a continuum that extends to microphthalmos and anophthalmos. Isolated colobomatous microphthalmos is inherited as an autosomal dominant trait in approximately 20% of cases. Parents of an affected child may have small, previously undetected chorioretinal or iris defects in an inferonasal location, so careful examination of family members is indicated.
Figure 20-11 Typical iris coloboma, right eye.
Atypical iris colobomas occur in areas other than the inferonasal quadrant and are not usually associated with posterior uveal colobomas. These colobomas probably result from fibrovascular remnants of the anterior hyaloid system and pupillary membrane.
Aniridia Aniridia is a panocular, bilateral disorder. The term aniridia is a misnomer, because at least a
rudimentary iris is always present. The degree of iris formation ranges from almost total absence to only mild hypoplasia, the latter of which can be confused with Axenfeld-Rieger syndrome. The typical presentation is an infant with nystagmus who appears to have absent irides or dilated, unresponsive pupils. Photophobia may be present. Examination findings commonly include small anterior polar cataracts, at times with attached strands of persistent pupillary membranes (Fig 20-12). Foveal hypoplasia is usually present, with visual acuity less than 20/100. Glaucoma and optic nerve hypoplasia are common. Corneal opacification often develops later in childhood and may lead to progressive deterioration of visual acuity. The corneal abnormality is due to a stem cell deficiency and therefore keratolimbal allograft stem cell transplantation may be a more effective treatment than corneal transplantation.
Figure 20-12 Aniridia in an infant. Both the ciliary processes and the edge of the lens are visible. Also present are persistent pupillary membrane fibers and a small central anterior polar cataract.