Congenital aniridia: etiology, manifestations and management

Abstract

Congenital aniridia manifests as total or partial absence of the iris caused most commonly by mutations in PAX6, FOXC1, PITX2, and CYP1B1. Recently two new genes, FOXD3 and TRIM44, have also been implicated in isolated studies. We discuss the genotype-phenotype correlations for the main implicated genes. Classic aniridia is a panocular condition, which includes aniridia, cataract, corneal pannus, foveal, and optic nerve hypoplasia associated with mutations in the PAX6 gene. Classical aniridia is due to PAX6 mutations, while other genes contribute to aniridia-like phenotypes. We review the challenges involved in the management of aniridia, and discuss various surgical interventions. The clinical importance of defining the genotype in cases of congenital aniridia has become acutely apparent with the advent of possible therapies for classical aniridia, which are discussed.

Keywords: aniridia; aniridia-associated keratopathy; cataract; congenital; goniotomy.

Figure 1.. Expression pattern of Pax6, FoxC1 and Pitx2 in the early and late eye

The expression patterns for Pax6, FoxC1, and Pitx2 are presented based on studies in mice and humans [–87]. Early expression is shown at embryonic day 11.5 (E11.5), which represents day 33 in human development, and late expression is shown at E18.5, which is close to prenatal in humans. For Pax6, early expression is seen in the lens vesicle (lv), optic cup (oc), and presumptive cornea (pc) [86]. Expression later in the prenatal is restricted to the ganglion cell layer and inner and outer portions of the inner nuclear layer of the retina (r), where the latter points to expression specifically in the amacrine and horizontal cells [85]. At this stage, Pax6 is also expressed in the epithelia of the cornea (c), conjunctiva (cj), lens (l), ciliary body (cb), iris (i) and trabecular meshwork (TM). For both FoxC1 and Pitx2, expression in the early eye is seen in the neural crest cells of the periocular mesenchyme that surrounds the oc, in the intracellular space between the lv and pc, and the intracellular space between the inner oc and lv [84]. In the prenatal eye, FoxC1 expression is reduced to the conjunctival epithelium, sclera and trabecular meshwork [82] and Pitx2 expression is reduced to the iris [83], and according to a study of expression in human eyes is expressed in the corneal epithelium, the ciliary body non-pigmented layer and the nuclear layers of the retina [87]. Pitx2 is present in the corneal stroma but FoxC1 is much reduced in this layer [82, 83].

Figure 2.. Aniridia showing absence of iris and peripheral pannus

Eye of 20-year-old female showing corneal and limbal changes. Indicated are presence of pannus and absence of a well demarcated limbus (white arrows), in addition to absence of the iris (small black arrows).

Figure 3.. Anterior polar cataract and subcapsular lens opacities

3-year-old male showing lens changes. Subcapsular opacity (small black arrow), anterior polar lens opacity (long black arrow) and absence of the iris (white arrow) are shown.

Figure 4.. Foveal hypoplasia in aniridia

Fundus photo of a 16-year-old boy. Note the blood vessels crossing the fovea (white arrow) and optic disc hypoplasia (black arrow).

Figure 5.. OCT of thickened fovea and absence of pit

OCT images of the same eye (Figure 4) showing absence of a foveal pit and a thickened fovea (black arrow).