Persistent pupillary membrane
Persistent pupillary membrane (Fig 21-12) is the most common developmental abnormality of the iris; it can be seen in approximately 95% of newborns. Remnants are common in older children and adults. Persistent pupillary membranes are rarely visually significant. If especially prominent, they can adhere to the anterior lens capsule, causing a small anterior polar cataract. They may be associated with other anterior segment abnormalities.
Iris hypoplasia refers to an underdeveloped iris stroma. It may be focal (iris coloboma) or diffuse (aniridia). If only the posterior pigment epithelium is underdeveloped, iris transillumination occurs.
Axenfeld-Rieger syndrome (ARS) is the commonest cause of iris (stromal) hypoplasia. Characteristic findings include posterior embryotoxon with attached iris strands and iris hypoplasia. These patients have a 50% lifetime risk of glaucoma (Figs 21-13, 21-14, 21-15). ARS is a spectrum that shows phenotypic and genetic heterogeneity. Conditions previously considered distinct—such as Axenfeld anomaly, Rieger anomaly or syndrome, iridogoniodysgenesis anomaly or syndrome, iris hypoplasia, and familial glaucoma iridogoniodysplasia—are now recognized as part of the spectrum of ARS.
Figure 21-12 Persistent pupillary membrane. Uncorrected visual acuity was 20/40.
Figure 21-13 Gonioscopic view in Axenfeld-Rieger syndrome.
Figure 21-14 Axenfeld-Rieger syndrome, bilateral.
Figure 21-15 Axenfeld-Rieger syndrome. Note variation compared with Figures 21-13 and 21-14.
(Courtesy of Jane D. Kivlin, MD.)
The features of ARS range from a smooth, cryptless iris surface to a phenotype that mimics aniridia. Examples include mild stromal thinning, marked atrophy with hole formation, corectopia, and ectropion uveae. Posterior embryotoxon, megalocornea (secondary to glaucoma), or microcornea may occur. Associated nonocular abnormalities include abnormal teeth, distinct facies, redundant periumbilical skin, hypospadias, cardiac valve abnormalities, and pituitary abnormalities. Heterozygous mutations in PITX2 or FOXC1, homeobox genes that regulate other ocular developmental genes, are the most common identifiable cause.
Iris transillumination results from the absence of pigment in the posterior epithelial layers (albinism) or from iris hypoplasia (as part of anterior segment dysgenesis, as in ARS). Iris transillumination has also been reported in Marfan syndrome, Prader-Willi 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.
Figure 21-16 Typical iris coloboma, right eye.
Coloboma of the iris
With a typical inferonasal iris coloboma, the pupil is shaped like a lightbulb, keyhole, or inverted teardrop (Fig 21-16). Typical colobomas may also involve the lens, ciliary body, choroid, retina, or optic nerve and are part of the MAC spectrum (discussed previously in this chapter). Parents of an affected child may have small, previously undetected chorioretinal or iris defects in an inferonasal location; thus, careful examination of family members is indicated.
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.
Classic aniridia is a panocular bilateral disorder. The term is a misnomer, however, because at least a rudimentary iris is always present. The degree of iris formation ranges from almost total absence to only mild hypoplasia, overlapping with ARS. The typical presentation is an infant with nystagmus who appears to have absent irides or dilated, unresponsive pupils. Examination findings commonly include small anterior polar lens opacities, at times with attached strands of persistent pupillary membranes (Fig 21-17). Foveal hypoplasia is usually present, with visual acuity often less than 20/100. Glaucoma, typically juvenile, 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; therefore, keratolimbal allograft stem cell transplantation may be a more effective treatment than corneal transplantation.
Figure 21-17 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.
Heterozygous PAX6 gene mutations (11p13) cause classic aniridia, particularly nonsense mutations (haploinsufficiency). Missense mutations are more likely associated with variable expressivity and partial phenotypes. Most (approximately two-thirds) aniridic children have the familial form. The PAX6 gene is a homeotic eye morphogenesis control gene involved in complex interactions between the optic cup, surface ectoderm, and neural crest during formation of the iris and other ocular structures.
Approximately one-third of aniridia cases result from new deletions that, if large enough, can also affect the contiguous WT1 gene (a contiguous gene syndrome); such patients are therefore at risk for Wilms tumor (nephroblastoma) before 5 years of age. This phenotype is part of the WAGR syndrome (Wilms tumor, aniridia, genitourinary malformations, and mental retardation). All children with sporadic aniridia should undergo chromosomal deletion analysis of 11p13 to exclude increased Wilms tumor risk. Familial aniridia does not carry a significant risk, although there have been rare reports of Wilms tumor associated with familial aniridia.
Congenital iris ectropion
Ectropion of the posterior pigment epithelium onto the anterior surface of the iris is sometimes termed ectropion uveae, but this is a misnomer because posterior iris epithelium is derived from neural ectoderm and is not considered part of the uvea. Congenital iris ectropion can occur as an acquired tractional abnormality, often associated with rubeosis iridis, or as a congenital nonprogressive abnormality, which can be associated with later glaucoma. It may occur in patients with neurofibromatosis, facial hemihypertrophy, or Prader-Willi syndrome. Congenital iris ectropion syndrome is a constellation of unilateral congenital iris ectropion, a glassy-smooth cryptless iris surface, a high iris insertion, dysgenesis of the drainage angle, and glaucoma risk, often with ptosis.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.